Gene Detail

Gene Symbol BRAF
Synonyms B-raf | B-RAF1 | BRAF1 | NS7 | RAFB1
Gene Description BRAF, serine/threonine-protein kinase B-raf, is a member of the Raf family of serine/threonine protein kinases, which signals through the MAP kinase pathway to regulate cell proliferation and cell growth (PMID: 24737949, PMID: 29540830). BRAF mutations have been identified in a variety of cancers, including, colorectal (PMID: 30122982), lung (PMID: 29729495), thyroid (PMID: 12970315), and melanoma (PMID: 24737949), and a number of mutations have also been demonstrated to confer drug resistance (PMID: 27478040).
Entrez Id 673
Chromosome 7
Map Location 7q34
Canonical Transcript NM_004333

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
V487_P492delinsA indel gain of function BRAF V487_P492delinsA results in a deletion of six amino acids near the alphaC-helix region of the kinase domain of the Braf protein combined with the insertion of one new amino acid in the same location (PMID: 26732095). V487_P492delinsA confers a gain of function to the Braf protein as indicated by increased pathway signaling and cell proliferation in culture (PMID: 26732095).
D594H missense loss of function - predicted BRAF D594H lies within the protein kinase domain of the Braf protein (UniProt.org). D594H results in a loss of Braf kinase activity, but leads to Ras-dependent activation of Erk signaling through CRAF (PMID: 28783719), and demonstrates decreased transforming activity compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785), and therefore is predicted to confer a loss of function to the Braf protein.
G478C missense loss of function - predicted BRAF G478C lies within the protein kinase domain of the Braf protein (UniProt.org). G478C demonstrates a lack of Braf kinase activity in cell culture (PMID: 22926515), and therefore is predicted to confer a loss of function to the Braf protein.
T599dup duplication gain of function BRAF T599dup (also referred to T599_V600insT) indicates the insertion of the duplicate amino acid, tyrosine (T)-599, in the protein kinase domain of the Braf protein (UniProt.org). T599dup confers a gain of function to the Braf protein as demonstrated by increased kinase activity and phosphorylation of downstream Mek and Erk, and is transforming in cell culture (PMID: 21190184).
V600R missense gain of function BRAF V600R (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600R confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity, downstream signaling, and the ability to transform cells in culture (PMID: 15035987, PMID: 29533785).
S364L missense no effect - predicted BRAF S364L lies within the protein kinase domain of the Braf protein (UniProt.org). S364L has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
E648Q missense loss of function - predicted BRAF E648Q lies within the protein kinase domain of the Braf protein (UniProt.org). E648Q has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture compared to wild-type Braf (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
A728V missense gain of function BRAF A728V (also referred to as A727V) does not lie within any known functional domains of the Braf protein (UniProt.org). A728V results in an intermediate increase in Braf kinase activity compared to wild-type Braf and increased Erk phosphorylation in cell culture (PMID: 15035987).
V681I missense no effect - predicted BRAF V681I lies within the protein kinase domain of the Braf protein (UniProt.org). V681I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
R509G missense no effect - predicted BRAF R509G lies within the protein kinase domain of the Braf protein (UniProt.org). R509C has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
S602F missense no effect - predicted BRAF S602F lies within the protein kinase domain of the Braf protein (UniProt.org). S602F has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
G469S missense gain of function BRAF G469S is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469S results in increased Erk phosphorylation (PMID: 27478040) and induces increased cell proliferation and cell viability compared to wild-type Braf in culture (PMID: 29533785).
L505H missense gain of function BRAF L505H lies within the protein kinase domain of the Braf protein (UniProt.org). L505H confers a gain of function to the Braf protein resulting in MEK/ERK activation and oncogenic transformation in cultured cells, and is associated with resistance to RAF inhibitors (PMID: 24283590). Y
G596D missense loss of function BRAF G596D lies within the protein kinase domain of the Braf protein (UniProt.org). G596D demonstrates decreased Braf kinase activity in cell culture (PMID: 28783719), and therefore is predicted to confer a loss of function to the Braf protein.
H585Y missense loss of function - predicted BRAF H585Y lies within the protein kinase domain of the Braf protein (UniProt.org). H585Y has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
act mut unknown gain of function BRAF act mut indicates that this variant results in a gain of function in the Braf protein. However, the specific amino acid change has not been identified.
L64I missense no effect - predicted BRAF L64I lies within the protein kinase domain of the Braf protein (UniProt.org). L64I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
R188T missense no effect - predicted BRAF R188T lies within the protein kinase domain of the Braf protein (UniProt.org). R188T has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
K601E missense gain of function BRAF K601E lies within the activation segment in the kinase domain of the Braf protein (PMID: 15343278). K601E results in increased Braf kinase activity and downstream activation of MEK and ERK in cell culture (PMID: 22798288, PMID: 28783719) and induces cell proliferation and cell viability in culture (PMID: 29533785).
D594G missense unknown BRAF D594G lies within the protein kinase domain of the Braf protein (UniProt.org). D594G has been demonstrated to result in impaired Braf kinase activity, but leads to increased activation of Erk signaling through CRAF in cell culture (PMID: 18794803, PMID: 28783719), however, has increased transforming ability in one of two cell lines in culture (PMID: 29533785), and therefore its effect on Braf protein function is unknown.
K698R missense no effect - predicted BRAF K698R lies within the protein kinase domain of the Braf protein (UniProt.org). K698R has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
V590I missense no effect - predicted BRAF V590I lies within the protein kinase domain of the Braf protein (UniProt.org). V590I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
P731S missense unknown BRAF P731S does not lie within any known functional domains of the Braf protein (UniProt.org). P731S has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
F294L missense no effect - predicted BRAF F294L lies within the protein kinase domain of the Braf protein (UniProt.org). F294L has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
fusion unknown unknown BRAF fusion indicates a fusion of the BRAF gene, but the fusion partner is unknown.
V600A missense no effect - predicted BRAF V600A (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600A results in phosphorylated Mek protein levels similar to wild-type Braf and therefore, is predicted to have no effect on Braf protein function (PMID: 26744778).
D594_T599dup duplication gain of function BRAF D594_T599dup (also referred to as T599_V600insDFGLAT) results in the insertion of six amino acids in the protein kinase domain of the Braf protein between amino acids 599 and 600 (UniProt.org).BRAF D594_T599dup results in increased colony formation and downstream Mek and Erk activation in cultured cells (PMID: 17297294).
V639I missense no effect - predicted BRAF V639I lies within the protein kinase domain of the Braf protein (UniProt.org). V639I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
L711F missense no effect - predicted BRAF L711F lies within the protein kinase domain of the Braf protein (UniProt.org). L711F has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
L485_P490del deletion gain of function BRAF L485_P490del results in the deletion of six amino acids within the beta-3/alpha-C helix loop in the protein kinase domain of the Braf protein (PMID: 26732095, UniProt.org). L485_P490del confers a gain of function to the Braf protein as demonstrated by increased kinase activity, phosphorylation of downstream Mek and Erk, and transformation ability in cell culture (PMID: 26732095, PMID: 26996308), and is associated with resistance to vemurafenib in cell culture (PMID: 26996308). Y
A762E missense unknown BRAF A762E lies within the protein kinase domain of the Braf protein (UniProt.org). A762E has not been biochemically characterized, but has been shown to confer resistance to Egfr inhibitors in culture (PMID: 27478040). Y
G469V missense gain of function BRAF G469V is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469V results in increased Braf kinase activity and activation of downstream MEK and ERK in cell culture (PMID: 28947956, PMID: 26343582, PMID: 28783719), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
G615R missense loss of function - predicted BRAF G615R lies within the protein kinase domain of the Braf protein (UniProt.org). G615R has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
V504I missense no effect - predicted BRAF V504I lies within the protein kinase domain of the Braf protein (UniProt.org). V504I has not been biochemically characterized, but results in similar cell proliferation and viability levels as wild-type Braf (PMID: 29533785).
K499N missense unknown BRAF K499N lies within the protein kinase domain of the Braf protein (UniProt.org). K449N has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
L245F missense unknown BRAF L245F does not lie within any known functional domains of the Braf protein (UniProt.org). L245F has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
G466E missense unknown BRAF G466E lies within the protein kinase domain of the Braf protein (UniProt.org). G466E results in impaired Braf kinase activity, but paradoxically increases Erk signaling through C-raf activation in cell culture and Xenopus embryos (PMID: 15035987), however, induces similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785), and therefore its effect on Braf protein function is unknown.
P490_Q494del deletion gain of function - predicted BRAF P490_Q494del results in the deletion of five amino acids near the alphaC-helix region of the protein kinase domain in the Braf protein from amino acids 490 to 494 (PMID: 26732095). P490_Q494del results in activation of Mek in cell culture (PMID: 26996308), and similar Braf deletions are activating (PMID: 26996308, PMID: 26732095), and therefore P490_Q494del is predicted to confer a gain of function to the Braf function.
V600E/K missense gain of function BRAF V600E/K indicates a mutation that results in the replacement of the valine (V) at amino acid 600 of the Braf protein by either a glutamate (E) or lysine (K). V600E/K mutations are hotspot mutations in Braf that result in increased Braf kinase activity (PMID: 15035987).
G596S missense unknown BRAF G596S lies within the protein kinase domain of the Braf protein (UniProt.org). G596S has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
G606A missense unknown BRAF G606A lies within the protein kinase domain of the Braf protein (UniProt.org). G606A has been identified in sequencing studies (PMID: 21825258), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
L597V missense gain of function BRAF L597V lies within the protein kinase domain of the Braf protein (UniProt.org). L597V results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288) and and induces cell proliferation and cell viability in culture (PMID: 29533785).
K601T missense gain of function - predicted BRAF K601T lies within the activation segment in the kinase domain of the Braf protein (PMID: 15343278). K601T results in increased Braf kinase activity in cell culture (PMID: 28783719), and in one of two cell lines increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and is therefore predicted to confer a gain of function to the Braf protein.
S467L missense unknown BRAF S467L lies with protein kinase domain of the Braf protein (UniProt.org). S467L results in impaired Braf kinase activity, but leads to Ras-dependent activation of Erk in cell culture (PMID: 28783719) and in two different cell lines, S467L increased cell proliferation and cell viability as compared to wild-type Braf (PMID: 29533785).
dec exp none no effect BRAF dec exp indicates decreased expression of the Braf protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
S637* nonsense loss of function - predicted BRAF S637* results in a premature truncation the Braf protein at amino acid 637 of 766 (UniProt.org). S637* has not been biochemically characterized, however, demonstrates an inability to induce cell viability and proliferation in cell culture (PMID: 29533785), and therefore is predicted to confer a loss of function to the Braf protein.
V471I missense unknown BRAF V471I lies within the protein kinase domain of the Braf protein (UniProt.org). V471I has been identified in sequencing studies (PMID: 23103869), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
S607F missense loss of function - predicted BRAF S607F lies within the protein kinase domain of the Braf protein (UniProt.org). S607F has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
W450* nonsense loss of function - predicted BRAF W450* results in a premature truncation the Braf protein at amino acid 450 of 766 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R450* is predicted to lead to a loss of Braf protein function.
G596C missense loss of function BRAF G596C lies within the protein kinase domain of the Braf protein (UniProt.org). G596C results in decreased Braf kinase activity, however, leads to activation of downstream MEK and ERK in combination with CRAF in cell culture (PMID: 27577079).
H574N missense no effect - predicted BRAF H574N lies within the protein kinase domain of the Braf protein (UniProt.org). H574N results in Erk phosphorylation at similar levels to wild-type Braf in culture (PMID: 27478040), and is therefore predicted to have no effect on Braf protein function.
V600delinsYM indel gain of function BRAF V600delinsYM results in a deletion of valine (V) at amino acid 600 within the protein kinase domain of the Braf protein, combined with the insertion of a tyrosine (Y) and a methionine (M) at the same site (UniProt.org). V600delinsYM results in increased Braf kinase activity, increased downstream signaling, and the ability to transform cells in culture (PMID: 22752848).
M517I missense loss of function - predicted BRAF M517I lies within the protein kinase domain of the Braf protein (UniProt.org). M517I has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
mutant unknown unknown BRAF mutant indicates an unspecified mutation in the BRAF gene.
T529I missense unknown BRAF T529I is a gatekeeper mutation that lies within the protein kinase domain of the Braf protein (PMID: 20538618). T529I has been demonstrated to result in resistance to Raf inhibitors in the context of BRAF V600E (PMID: 20538618), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Jun 2018). Y
I582M missense unknown BRAF I582M lies within the protein kinase domain of the Braf protein (UniProt.org). I582M has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
P348T missense no effect - predicted BRAF P348T lies within the protein kinase domain of the Braf protein (UniProt.org). P348T has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
L678I missense loss of function - predicted BRAF L678I lies within the protein kinase domain of the Braf protein (UniProt.org). L678I has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
L584F missense unknown BRAF L584F lies within the protein kinase domain of the Braf protein (UniProt.org). L584F has not been biochemically characterized but, in one of two cell lines, increased cell proliferation and cell viability as compared to wild-type Braf (PMID: 29533785).
G606W missense loss of function - predicted BRAF G606W lies within the protein kinase domain of the Braf protein (UniProt.org). G606W has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
W604del deletion unknown BRAF W604del results in the deletion of an amino acid in the protein kinase domain of the Braf protein at amino acid 604 (UniProt.org). W604del has been identified in sequencing studies (PMID: 15513360), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G466A missense unknown BRAF G466A (also reported as G465A) lies within the protein kinase domain of the Braf protein (UniProt.org). The functional effect of G466A on Braf is unclear as it has been characterized both as having intermediate Braf kinase activity (PMID: 15035987) and low Braf kinase activity (PMID: 28783719), leads to Ras-dependent activation of downstream Erk in cell culture (PMID: 28783719), and in one of two cell lines increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
P367S missense unknown BRAF P367S does not lie within any known functional domains within the Braf protein (UniProt.org). P367S has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785).
T241P missense unknown BRAF T241P does not lie within any known functional domains of the Braf protein (UniProt.org). T241P is only weakly activating of MEK and ERK and does not induce transformation in cell culture (PMID: 19206169), but in one of two cell lines, T241P did increase cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
T401I missense no effect - predicted BRAF T401I lies within the protein kinase domain of the Braf protein (UniProt.org). T401I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
E611D missense unknown BRAF E611D lies within the protein kinase domain of the Braf protein (UniProt.org). E611D has been identified in sequencing studies (PMID: 15935100), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
V600E missense gain of function BRAF V600E (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600E confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity, downstream signaling, and the ability to transform cells in culture (PMID: 15035987, PMID: 29533785).
K601I missense unknown BRAF K601I lies within the protein kinase domain of the Braf protein (UniProt.org). K601I has been identified in sequencing studies (PMID: 23555633), but has not been biochemically characterized and therefore its effect on Braf protein function is unknown (PubMed, Sep 2018).
N581K missense loss of function - predicted BRAF N581K lies within the protein kinase domain of the Braf protein (UniProt.org). N581K has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
G464R missense gain of function BRAF G464R (also reported as G463R) lies within the protein kinase domain of the Braf protein (UniProt.org). G464R results in increased Braf kinase activity, increased downstream Erk signaling (PMID: 15046639), and induces cell proliferation and cell viability in culture (PMID: 29533785).
G466R missense loss of function - predicted BRAF G466R (previously reported as G465R) lies within the glycine-rich loop in the protein kinase domain of the Braf protein (PMID: 14681681). G466R results in impaired Braf kinase activity, but activates Erk signaling in cell culture (PMID: 15046639), and in one of two cell lines, G466R decreased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
L514V missense unknown BRAF L514V lies within the protein kinase domain of the Braf protein (UniProt.org). L514V results in enhanced dimerization when expressed in cis with BRAF V600E in culture, and is associated with resistance to Raf inhibitors, but has not been individually characterized and therefore, its effect on Braf protein function is unknown (PMID: 29880583). Y
V459L missense unknown BRAF V459L lies with protein kinase domain of the Braf protein (UniProt.org). V459L results in impaired Braf kinase activity, leads to Ras-dependent activation of Erk in cell culture (PMID: 28783719), but in two different cell lines, induced similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785).
V600dup duplication gain of function BRAF V600dup (also referred to as T599_V600insV) indicates the insertion of the duplicate amino acid, valine (V)-600, in the protein kinase domain of the Braf protein (UniProt.org). V600dup confers a gain of function to the Braf protein as demonstrated by increased kinase activity and phosphorylation of downstream Mek and Erk, and is transforming in cell culture (PMID: 21190184).
W604G missense unknown BRAF W604G lies within the protein kinase domain of the Braf protein (UniProt.org). W604G has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
R444W missense unknown BRAF R444W does not lie within any known functional domains of the Braf protein (UniProt.org). R444W has been identified in sequencing studies (PMID: 15578519), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
V600L missense unknown BRAF V600L (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600L increased cell proliferation and cell viability compared to wild-type Braf one of two cell lines in culture (PMID: 29533785), however, has not been biochemically characterized and therefore, its effect on Braf function is unknown.
A762V missense no effect - predicted BRAF A762V lies within the protein kinase domain of the Braf protein (UniProt.org). A762V has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
N581D missense no effect - predicted BRAF N581D lies within the protein kinase domain of the Braf protein (UniProt.org). N581D results in transactivation of ELK at comparable levels to wild-type Braf in a reporter assay (PMID: 16474404), and is therefore predicted to have no effect on Braf protein function.
P407L missense no effect - predicted BRAF P407L lies within the protein kinase domain of the Braf protein (UniProt.org). P407L has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
N581S missense unknown BRAF N581S lies within the protein kinase domain of the Braf protein (UniProt.org). N581S has been demonstrated to result in intermediate Braf kinase activity (PMID: 15035987), as well low Braf kinase activity (PMID: 28783719), and results in Ras-dependent activation of ERK signaling in cell culture (PMID: 28783719), however in another study, N581S demonstrated increased transformation ability in one of two different cell lines as compared to wild-type Braf (PMID: 29533785).
H574Q missense gain of function BRAF H574Q lies within the protein kinase domain of the Braf protein (UniProt.org). H574Q confers a gain of function to the Braf protein as indicated by increased Erk phosphorylation in culture and tumor formation in animal models, and confers resistance to Egfr inhibitors in culture (PMID: 27478040). Y
D587E missense unknown BRAF D578E lies within the protein kinase domain of the Braf protein (UniProt.org). D587E has been identified in sequencing studies (PMID: 15935100), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
I592V missense unknown BRAF I592V lies within the protein kinase domain of the Braf protein (UniProt.org). I592V has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G258V missense unknown BRAF G258V lies within the protein kinase domain of the Braf protein (UniProt.org). G258V has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
L597P missense unknown BRAF L597P lies within the protein kinase domain of the Braf protein (UniProt.org). L597P has been identified in sequencing studies (PMID: 24714776), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown.
R271H missense no effect - predicted BRAF R271H lies within the protein kinase domain of the Braf protein (UniProt.org). R271H has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
R603* nonsense loss of function - predicted BRAF R603* results in a premature truncation within the protein kinase domain of the Braf protein at amino acid 603 of 766 (UniProt.org, PMID: 11032810). Due to the loss of the protein kinase domain (UniProt.org, PMID: 11032810), R603* is predicted to lead to a loss of function.
D594A missense loss of function BRAF D594A lies within the protein kinase domain of the Braf protein (UniProt.org). D594A results in a lack of Braf kinase activity (PMID: 20141835, PMID: 20978199, PMID: 28783719), promotes aneupolidy (PMID: 20978199), and in one of two cell lines demonstrated decreased transformation ability compared to wild-type Braf in culture (PMID: 29533785), but leads to activation of Mek and Erk through cooperation with activated RAS and transactivation of CRAF in cell culture and mouse models (PMID: 20141835, PMID: 20978199, PMID: 28783719).
S605F missense unknown BRAF S605F lies within the protein kinase domain of the Braf protein (UniProt.org). S605F has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G469L missense unknown BRAF G469L is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469L has been identified in the scientific literature (PMID: 24035431, PMID: 26301799), but has not been biochemically characterized, and therefore, its effect on Braf protein function is unknown (PubMed, Sep 2018).
F259L missense no effect - predicted BRAF F259L lies within the protein kinase domain of the Braf protein (UniProt.org). F259L has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
Q262R missense unknown BRAF Q262R lies within the phorbol-ester/DAG-type zinc finger region of the Braf protein (UniProt.org). Q262R has not been characterized in the scientific literature and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
A598T missense loss of function - predicted BRAF A598T lies within the protein kinase domain of the Braf protein (UniProt.org). A598T demonstrates a lack of Braf kinase activity in culture (PMID: 22926515), and therefore, is predicted to result in a loss of Braf protein function.
K483M missense unknown BRAF K483M (also reported as K482M) lies within an ATP binding site in the protein kinase domain of the Braf protein (UniProt.org). K483M results in a loss of Braf kinase activity, however, has been demonstrated to both activate MEK through CRAF (PMID: 16508002, PMID: 23533272), and lack ability to activate ERK and CRAF in cell culture and in Xenopus (PMID: 15035987).
N581I missense unknown BRAF N581I lies within the protein kinase domain of the Braf protein (UniProt.org). N581I results in low Braf kinase activity and Ras-dependent activation of Erk signaling in cell culture (PMID: 28783719) but, induces similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785).
S419Y missense no effect - predicted BRAF S419Y lies within the protein kinase domain of the Braf protein (UniProt.org). S419Y has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
H269Y missense unknown BRAF H269Y lies within the protein kinase domain of the Braf protein (UniProt.org). H269Y has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
T470K missense no effect - predicted BRAF T470K lies within the protein kinase domain of the Braf protein (UniProt.org). T470K has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
D594Y missense unknown BRAF D594Y lies within the protein kinase domain of the Braf protein (UniProt.org). D594Y has been identified in sequencing studies (PMID: 28486044), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Sep 2018).
P403fs frameshift loss of function - predicted BRAF P403fs results in a change in the amino acid sequence of the Braf protein beginning at aa 403 of 766, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), P403fs is predicted to lead to a loss of Braf protein function.
K601del deletion unknown BRAF K601del results in the deletion of an amino acid in the protein kinase domain of the Braf protein at amino acid 601 (UniProt.org). K601del has been identified in sequencing studies (PMID: 19152441), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
K483E missense unknown BRAF K483E lies within the protein kinase domain of the Braf protein (UniProt.org). K483E has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785).
V600X missense gain of function - predicted BRAF V600X indicates any Braf missense mutation that results in replacement of the the valine (V) at amino acid 600 by a different amino acid. BRAF V600 mutations are hotspot mutations that often result in increased Braf kinase activity (PMID: 15035987).
P453T missense unknown BRAF P453T does not lie within any known functional domains of the Braf protein (UniProt.org). P453T has been identified in sequencing studies (PMID: 16404419), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
D594E missense loss of function BRAF D594E lies within the protein kinase domain of the Braf protein (UniProt.org). D594E results in impaired Braf kinase activity, however, results in increased Mek and Erk phosphorylation in the presence of CRAF in cell culture (PMID: 28783719).
V600G missense gain of function BRAF V600G (previously reported as V599G) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600G confers a gain of function to Braf as indicated by increased phosphorylation of MEK and ERK and activation of ELK in culture (PMID: 20735442, PMID: 26744778), and in one of two cell lines, increased cell proliferation and viability compared to wild-type Braf (PMID: 29533785).
P162S missense no effect - predicted BRAF P162S lies within the protein kinase domain of the Braf protein (UniProt.org). P162S has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
L597Q missense gain of function BRAF L597Q lies within the protein kinase domain of the Braf protein (UniProt.org). L597Q results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288) and induces cell proliferation and cell viability in culture (PMID: 29533785).
wild-type none no effect Wild-type BRAF indicates that no mutation has been detected within the BRAF gene.
L485_Q494del deletion gain of function - predicted BRAF L485_Q494del results in the deletion of ten amino acids within the beta-3/alpha-C helix loop in the protein kinase domain of the Braf protein (PMID: 26732095, UniProt.org). L485_Q494del has not been characterized, however, is predicted to result in a gain of function due to other characterized BRAF deletions in the same region (PMID: 26732095).
L597S missense gain of function BRAF L597S lies within the protein kinase domain of the Braf protein (UniProt.org). L597S results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288) and induces cell proliferation and cell viability in culture (PMID: 29533785).
A712T missense no effect - predicted BRAF A712T lies within the protein kinase domain of the Braf protein (UniProt.org). A712T has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
V504_R506dup duplication gain of function BRAF V504_R506dup (also referred to as R506_K507insVLR) lies within the protein kinase domain (UniProt.org). V504_R506dup confers a gain of function to the Braf protein as demonstrated by stabilization of Braf homodimers and increased downstream Erk phosphorylation in cultured cells (PMID: 23817572), and is associated with increased Erk1/2 phosphorylation in human tumor samples (PMID: 29544532).
A320T missense no effect - predicted BRAF A320T lies within the protein kinase domain of the Braf protein (UniProt.org). A320T has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
inact mut unknown loss of function BRAF inact mut indicates that this variant results in a loss of function of the Braf protein. However, the specific amino acid change has not been identified.
G464V missense gain of function BRAF G464V (also reported as G463V) lies within the protein kinase domain of the Braf protein (UniProt.org). G464V results in increased Braf kinase activity and increased downstream Mek and Erk activation (PMID: 12068308, PMID: 26343582), and in one of two cell lines, increased cell proliferation and viability compared to wild-type Braf in culture (PMID: 29533785).
L597R missense gain of function BRAF L597R lies within the protein kinase domain of the Braf protein (UniProt.org). L597R results in activation of Braf as indicated by increased phosphorylation of Mek and Erk in cell culture (PMID: 22798288, PMID: 26343582), is associated with Erk activation in a patient tumor sample (PMID: 23715574), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
A598_T599insV insertion gain of function BRAF A598_T599insV results in the insertion of a valine (V) in the protein kinase domain of the Braf protein between amino acids 598 and 599 (UniProt.org). A598_T599insV results in increased Braf kinase activity, increased downstream Mapk and Mek signaling, and the ability to transform cells in culture (PMID: 16501605).
Y472C missense unknown BRAF Y472C lies within the protein kinase domain of the Braf protein (UniProt.org), Y472C results in impaired Braf kinase activity, however, paradoxically activates Mek and Erk through transactivation of CRAF (PMID: 22649091), but in two different cell lines, Y472C induced similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785).
R462K missense no effect - predicted BRAF R462K lies within the protein kinase domain of the Braf protein (UniProt.org). R462K has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
T599I missense gain of function BRAF T599I (also reported as T598I) lies within the protein kinase domain of the Braf protein (UniProt.org). T599I results in increased Braf kinase activity, increased downstream Erk signaling (PMID: 15035987), and induces cell proliferation and cell viability in culture (PMID: 29533785).
G606E missense unknown BRAF G606E lies within the protein kinase domain of the Braf protein (UniProt.org). G606E has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
T529N missense unknown BRAF T529N is a gatekeeper mutation that lies within the protein kinase domain of the Braf protein (PMID: 20538618). T529N has been demonstrated to result in resistance to Raf inhibitors in the context of BRAF V600E (PMID: 20538618), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Jun 2018). Y
F595S missense unknown BRAF F595S lies within the protein kinase domain of the Braf protein (UniProt.org). F595S has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
T488_Q493delinsK indel gain of function - predicted BRAF T488_Q493delinsK results in the deletion of six amino acids near the alphaC-helix region of the Braf protein kinase domain combined with the insertion of one new amino acid in the same location (PMID: 26732095). T488_Q493delinsK has not been characterized, however, is predicted to result in a gain of function due to other characterized BRAF deletions in the same region (PMID: 26732095).
L618F missense loss of function - predicted BRAF L618F lies within the protein kinase domain of the Braf protein (UniProt.org). L618F has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
G469A missense gain of function BRAF G469A is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469A results in increased Braf kinase activity and downstream activation of Erk, and is transforming in cell culture (PMID: 19010912, PMID: 12068308, PMID: 29533785).
N486_P490del deletion gain of function BRAF N486_P490del results in the deletion of five amino acids near the alphaC-helix region of the kinase domain (PMID: 26732095). N486_P490del confers a gain of function to the Braf protein as indicated by activation of the MAPK signaling pathway and increased cell proliferation in culture (PMID: 26732095).
P676S missense no effect - predicted BRAF P676S lies within the protein kinase domain of the Braf protein (UniProt.org). P676S has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
T529M missense unknown BRAF T529M is a gatekeeper mutation that lies within the protein kinase domain of the Braf protein (PMID: 20538618). T529M has been demonstrated to result in resistance to Raf inhibitors in the context of BRAF V600E (PMID: 20538618), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Jun 2018). Y
N486D missense unknown BRAF N486D lies within the protein kinase domain of the Braf protein (UniProt.org). N486D has not been biochemically characterized, but is results in increased transformation ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785).
R389C missense no effect - predicted BRAF R389C lies within the protein kinase domain of the Braf protein (UniProt.org). R389C has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
W619R missense unknown BRAF W619R lies within the protein kinase domain of the Braf protein (UniProt.org). W619R has been identified in sequencing studies (PMID: 16179870), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
L485_P490delinsY indel gain of function - predicted BRAF L485_P490delinsY results in a deletion of six amino acids near the alphaC-helix region of the Braf protein kinase domain combined with the insertion of one new amino acid in the same location (PMID: 26732095). L485_P490delinsY is associated with increased MEK/ERK activation in cells also harboring L485_P490delinsF, and similar deletions result in Braf activation (PMID: 26732095), and therefore, L485_P490delinsY is predicted to confer a gain of function to the Braf protein.
G469R missense gain of function - predicted BRAF G469R is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). G469R demonstrates intermediate BRAF kinase activity (PMID: 28783719) and results in constitutive ERK activation in cell culture (PMID: 24920063), and in one of two cell lines leads to increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and is therefore predicted to confer a gain of function to the Braf protein.
N581T missense no effect - predicted BRAF N581T lies within the protein kinase domain of the Braf protein (UniProt.org). N581T has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
I592M missense unknown BRAF I592M lies within the protein kinase domain of the Braf protein (UniProt.org). I592M has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
L613F missense unknown BRAF L613F lies within the protein kinase domain of the Braf protein (UniProt.org). L613F has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785).
V600_K601delinsE indel gain of function BRAF V600_K601delinsE results in the deletion of two amino acids formation of a new glutamic acid (E) residue in the protein kinase domain of the Braf protein between amino acids 600 and 601 (UniProt.org, PMID: 22563563). V600_K601delinsE leads to activation of downstream Mek and Erk signaling, increased colony formation (PMID: 17297294), and induces cell proliferation and cell viability in cell culture (PMID: 29533785).
D380H missense no effect - predicted BRAF D380H lies within the protein kinase domain of the Braf protein (UniProt.org). D380H has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
E275K missense unknown BRAF E275K lies within the phorbol-ester/DAG-type zinc finger region of the Braf protein (UniProt.org). E275K confers a loss of function on the Braf protein as indicated by decreased activation of Mek and Erk in cell culture (PMID: 19206169), however, demonstrates similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785).
R462I missense unknown BRAF R462I lies within the protein kinase domain of the Braf protein (UniProt.org). R462I results in activation of Braf and increased Erk signaling in cell culture (PMID: 15035987) but, in two different cell lines, induced similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785).
H608R missense unknown BRAF H608R lies within the protein kinase domain of the Braf protein (UniProt.org). H608R has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
L485F missense gain of function BRAF L485F lies within the protein kinase domain of the Braf protein (UniProt.org). L485F confers a gain of function to the Braf protein as demonstrated by increased kinase activity and activation of downstream Mek and Erk in cell culture (PMID: 16439621), and in one of two cell lines, L485F increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785).
G464E missense gain of function BRAF G464E (also reported as G463E) lies within the protein kinase domain of the Braf protein (UniProt.org). G464E results in increased Braf kinase activity and activation of MEK and ERK (PMID: 15035987, PMID: 23680146), and in one of two cell lines, increased cell proliferation and cell viability compared to wild-type Braf in culture (PMID: 29533785).
A598S missense unknown BRAF A598S lies within the protein kinase domain of the Braf protein (UniProt.org). A598S has not been characterized in the scientific literature and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G469E missense unknown BRAF G469E is a hotspot mutation within the protein kinase domain of the Braf protein (UniProt.org). The functional effect of G469E on Braf is unclear as it has been characterized as having both low Braf kinase activity (PMID: 28783719) and intermediate Braf kinase activity (PMID: 15035987), results in Ras-dependent activation of ERK signaling in cell culture (PMID: 28783719), and in one of two cell lines, G469E increased cell proliferation and cell viability as compared to wild-type Braf (PMID: 29533785).
I463T missense unknown BRAF I463T lies within the protein kinase domain of the BRAF protein (UniProt.org). I463T has been identified in the scientific literature (PMID: 28829677), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
T599_V600insEAT insertion gain of function - predicted BRAF T599_V600insEAT results in the insertion of 3 amino acids in the protein kinase domain of the Braf protein between amino acids 599 and 600 (UniProt.org). T599_V600insEAT has not been characterized, however other insertions between T599 and V600 are activating thus, T599_V600insEAT is predicted to lead to a gain of Braf protein function (PMID: 16501605, PMID: 17297294, PMID: 21190184).
H568D missense loss of function BRAF H568D lies within the protein kinase domain of the Braf protein (UniProt.org). H568D results in a loss of Braf kinase activity in cell culture (PMID: 29666306).
N20T missense unknown BRAF N20T does not lie within any known functional domains of the Braf protein (UniProt.org). N20T has not been characterized in the scientific literature and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
V600K missense gain of function BRAF V600K (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600K confers a gain of function to the Braf protein as demonstrated by increased kinase activity, downstream signaling, and the ability to transform cells in vitro (PMID: 15035987, PMID: 29533785).
G469del deletion loss of function BRAF G469del results in the deletion of an amino acid in the protein kinase domain of the Braf protein at amino acid 469 (UniProt.org). G469del demonstrates decreased Braf kinase activity, does not activate downstream ERK, and is minimally transforming in cell culture (PMID: 23833300).
V600M missense gain of function - predicted BRAF V600M (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600M results in intermediate Braf kinase activity in cell culture (PMID: 28783719), and in one of two cell lines increased cell proliferation and cell viability compared to wild-type Braf (PMID: 29533785), and is therefore predicted to confer a gain of function to the Braf protein.
M53I missense unknown BRAF M53I does not lie within any known functional domains of the Braf protein (UniProt.org). M53I has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
S605G missense unknown BRAF S605G lies within the protein kinase domain of the Braf protein (UniProt.org). S605G has been identified in sequencing studies (PMID: 16773193, PMID: 20635392), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
P141L missense no effect - predicted BRAF P141L lies within the protein kinase domain of the Braf protein (UniProt.org). P141L has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
T599R missense gain of function BRAF T599R lies within the activation loop in the kinase domain of the Braf protein (PMID: 19206169). T599R confers a gain of function on Braf, as indicated by increased MEK and ERK phosphorylation, and is transforming in cell culture (PMID: 19206169, PMID: 29533785).
G104E missense no effect - predicted BRAF G104E lies within the protein kinase domain of the Braf protein (UniProt.org). G104E has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
T599A missense loss of function BRAF T599A lies within the protein kinase domain of the Braf protein (UniProt.org). T599A does not result in increased MEK or ERK phosphorylation and does not transactivate CRAF (PMID: 22506009), and demonstrates decreased transformation ability compared to wild-type Braf in cell culture (PMID: 29533785).
Q257H missense unknown BRAF Q257H lies within the phorbol-ester/DAG-type zinc finger region of the Braf protein (UniProt.org). Q257H has been identified in sequencing studies (PMID: 28852190), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G596fs frameshift loss of function - predicted BRAF G596fs results in a change in the amino acid sequence of the Braf protein beginning at aa 596 of 766, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the protein kinase domain (UniProt.org), G596fs is predicted to lead to a loss of Braf protein function.
R509H missense loss of function BRAF R509H lies within the dimerization interface region of the Braf protein (PMID: 22510884). R509H confers a loss of function to the Braf protein, as demonstrated by decreased Braf dimerization and reduced ability to activate downstream Mek signaling in in vitro assays (PMID: 22510884).
R671Q missense no effect - predicted BRAF R671Q lies within the protein kinase domain of the Braf protein (UniProt.org). R671Q has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
D594V missense loss of function BRAF D594V lies within the protein kinase domain of the Braf protein (UniProt.org). D594V results in impaired Braf kinase activity, and decreased activation of Erk, Mek, and CRAF in cell culture (PMID: 28947956, PMID: 15035987), and has decreased transforming ability in one of two cell lines compared to wild-type Braf in culture (PMID: 29533785).
F468C missense gain of function BRAF F468C (also referred to as F467C) lies within the protein kinase domain of the Braf protein (UniProt.org). F468C confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity and downstream Erk phosphorylation, activation of NFkappaB signaling in reporter assays, and transformation of cultured cells (PMID: 15150094).
F247L missense gain of function BRAF F247L lies within the phorbol-ester/DAG-type zinc finger region of the Braf protein (UniProt.org). F247L confers a gain of function to Braf, as indicated by activation of downstream MAPK signaling and is transforming in cultured cells (PMID: 28512244, PMID: 29533785).
V600D missense gain of function BRAF V600D (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600D confers a gain of function to the Braf protein as demonstrated by increased kinase activity, downstream signaling, and the ability to transform cells in vitro (PMID: 15035987).
G421V missense no effect - predicted BRAF G421V lies within the protein kinase domain of the Braf protein (UniProt.org). G421V has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
P367R missense gain of function BRAF P367R does not lie within any known functional domains within the Braf protein (UniProt.org). P367R confers a gain of function to the Braf protein as indicated by increased Erk phosphorylation in culture and tumor formation in animal models, and demonstrates resistance to Egfr inhibitors in culture (PMID: 27478040). Y
D587G missense unknown BRAF D587G lies within the protein kinase domain of the Braf protein (UniProt.org). D587G has not been characterized in the scientific literature and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
E228V missense no effect - predicted BRAF E228V lies within the protein kinase domain of the Braf protein (UniProt.org). E228V has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
amp none no effect BRAF amplification indicates an increased number of copies of the Braf gene. However, the mechanism causing the increase is unspecified.
K601Q missense gain of function BRAF K601Q lies within the activation loop in the kinase domain of the Braf protein (PMID: 19206169). K601Q confers a gain of function on Braf, as indicated by increased MEK and ERK phosphorylation, and is transforming in cell culture (PMID: 19206169, PMID: 29533785).
A598_T599insARC insertion gain of function - predicted BRAF A598_T599insARC results in the insertion of 3 amino acids in the protein kinase domain of the Braf protein between amino acids 598 and 599 (UniProt.org). BRAF A598_T599insARC has not been characterized, however other insertions between A598 and T599 are activating thus, A598_T599insARC is predicted to lead to a gain of Braf protein function (PMID: 16501605).
W531C missense unknown BRAF W531C lies within the protein kinase domain of the Braf protein (UniProt.org). W531I demonstrates activity and transformation ability comparable to wild-type Braf in cultured cells (PMID: 19206169) but, also demonstrated increased cell proliferation and viability in two different cell lines as compared to wild-type Braf (PMID: 29533785).
G596R missense loss of function - predicted BRAF G596R lies within the protein kinase domain of the Braf protein, within the DFG motif (PMID: 19735675). G596R results in impaired Braf kinase activity and decreased Mek and Erk phosphorylation, including in the presence of BRAF V600E, is not transforming in culture and does not promote tumor formation in mouse models, but results in activation of Erk in the presence of CRAF (PMID: 19735675, PMID: 28783719), however, in another study demonstrates similar cell proliferation and viability levels to wild-type Braf (PMID: 29533785), and is predicted to confer a loss of function to the Braf protein.
K205Q missense no effect - predicted BRAF K205Q lies within the protein kinase domain of the Braf protein (UniProt.org). K205Q has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
Y656D missense loss of function - predicted BRAF Y656D lies within the protein kinase domain of the Braf protein (UniProt.org). Y656D has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture (PMID: 29533785), and is therefore predicted to confer a loss of function to the Braf protein.
N581Y missense unknown BRAF N581Y lies within the protein kinase domain of the Braf protein (UniProt.org). N581Y has been identified in the scientific literature (PMID: 19474002, PMID: 26084293), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Nov 2018).
R719S missense no effect - predicted BRAF R719S lies within the protein kinase domain of the Braf protein (UniProt.org). R719S has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
A598V missense gain of function - predicted BRAF A598V lies within the protein kinase domain of the Braf protein (UniProt.org). A598V is associated with increased activation of Braf and downstream Mek and Erk in human tumor samples (PMID: 19200582), and is therefore predicted to confer a gain of function to the Braf protein.
E586K missense gain of function BRAF E586K (also reported as E585K) lies within the protein kinase domain of the Braf protein (UniProt.org). E586K results in increased Braf kinase activity, and activation of Mek and Erk in cell culture (PMID: 15035987, PMID: 22510884), and increases cell proliferation and viability compared to wild-type Braf in one of two cell lines (PMID: 29533785).
P341S missense no effect - predicted BRAF P341S lies within the protein kinase domain of the Braf protein (UniProt.org). P341S has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
G466V missense loss of function BRAF G466V lies within the protein kinase domain of the Braf protein (UniProt.org). G466V results in impaired Braf kinase activity, but paradoxically activates MEK and ERK through transactivation of CRAF in cell culture (PMID: 22649091, PMID: 28783719), and in one of two cell lines, G466V decreased cell proliferation and cell viability as compared to wild-type Braf (PMID: 29533785).
K499E missense gain of function BRAF K499E lies within the protein kinase domain of the Braf protein (UniProt.org). K499E confers a gain of function to the Braf protein as demonstrated by increased Braf kinase activity and downstream signaling, activation of ELK-dependent signaling in reporter assays, and foci formation in cultured cells (PMID: 16474404, PMID: 18413255, PMID: 26065894).
S467A missense gain of function BRAF S467A lies within the protein kinase domain of the Braf protein (UniProt.org). S467A confers a gain of function to the Braf protein as demonstrated by increased kinase activity and activation of downstream Mek signaling (PMID: 23680146, PMID: 16439621).
rearrange unknown unknown BRAF rearrangement indicates an unspecified rearrangement of the BRAF gene.
T599_V600insTT insertion gain of function BRAF T599_V600insTT results in the insertion of two threonines (T) in the protein kinase domain of the Braf protein between amino acids 599 and 600 (UniProt.org). T599_V600insTT results in increased Braf kinase activity in an in vitro assay, and increased downstream Mek/Erk signaling in culture (PMID: 21190184).
E501K missense unknown BRAF E501K lies within the protein kinase domain of the Braf protein (UniProt.org). E501K results in ELK transactivation at comparable levels to wild-type Braf in a reporter assay (PMID: 16474404), however, also demonstrates decreased Braf kinase activity in culture (PMID: 17603482), and therefore, its effect on Braf protein function is unknown.
I463S missense gain of function BRAF I463S lies within the protein kinase domain of the Braf protein (UniProt.org). I463S results in an intermediate increase in Braf kinase activity compared to wild-type Braf and increased Erk activation in cell culture (PMID: 15035987).
W604R missense unknown BRAF W604R lies within the protein kinase domain of the Braf protein (UniProt.org). W604R has been identified in sequencing studies (PMID: 21825258, PMID: 23833300), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
G606V missense unknown BRAF G606V lies within the protein kinase domain of the Braf protein (UniProt.org). G606V has been identified in sequencing studies (PMID: 21825258), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
R347* nonsense loss of function - predicted BRAF R347* results in a premature truncation of the of the 766 aa Braf protein at aa 347 (UniProt.org). Due to the loss of a portion of the protein kinase domain (UniProt.org), R347* is predicted to lead to a loss of Braf protein function.
N49I missense no effect - predicted BRAF N49I lies within the protein kinase domain of the Braf protein (UniProt.org). N49I has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
L485Y missense unknown BRAF L485Y lies within the protein kinase domain of the Braf protein (UniProt.org). L485Y has been demonstrated to confer Raf inhibitor resistance to in cell culture (PMID: 19276360), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Jun 2018). Y
L485W missense unknown BRAF L485W lies within the protein kinase domain of the Braf protein (UniProt.org). L485W has not been biochemically characterized, but in one of two cell lines, induced similar cell proliferation and cell viability as wild-type Braf (PMID: 29533785).
Q609H missense no effect - predicted BRAF Q609H lies within the protein kinase domain of the Braf protein (UniProt.org). Q609H has not been biochemically characterized, but results in similar cell proliferation and viability levels to wild-type Braf in culture (PMID: 29533785), and therefore is predicted to have no effect on Braf protein function.
E695K missense unknown BRAF E695K lies within the protein kinase domain of the Braf protein (UniProt.org). E695K has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
Q257R missense gain of function BRAF Q257R lies within the phorbol-ester/DAG-type zinc finger region of the BRAF protein (UniProt.org). Q257R confers a gain of function to the Braf protein as demonstrated by increased kinase activity and activation of downstream Mek signaling in cell cuture, and activation of ELK in reporter assays (PMID: 16474404, PMID: 16439621).
S605N missense unknown BRAF S605N lies within the protein kinase domain of the Braf protein (UniProt.org). S605N has been identified in sequencing studies (PMID: 15331929), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
V600fs frameshift loss of function - predicted BRAF V600fs results in a change in the amino acid sequence of the Braf protein beginning at aa 600 of 766, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the disruption of the protein kinase domain, V600fs is predicted to lead to a loss of Braf protein function (UniProt.org).
T599_V600insETT insertion gain of function - predicted BRAF T599_V600insETT results in the insertion of 3 amino acids in the protein kinase domain of the Braf protein between amino acids 599 and 600 (UniProt.org). BRAF T599_V600insETT has not been characterized, however other insertions between T599 and V600 are activating thus, T599_V600insETT is predicted to lead to a gain of Braf protein function (PMID: 16501605, PMID: 17297294, PMID: 21190184).
K601N missense gain of function BRAF K601N lies within the protein kinase domain of the Braf protein (UniProt.org). K601N confers a gain of function on Braf, as indicated by increased phosphorylation of MEK and ERK in cell in culture (PMID: 24434212) and induction of cell proliferation and cell viability in culture (PMID: 29533785).
Y538H missense unknown BRAF Y538H lies within the protein kinase domain of the Braf protein (Uniprot.org). Y538H has not been characterized in the scientific literature and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
E501G missense loss of function BRAF E501G lies within the protein kinase domain of the Braf protein (UniProt.org). E501G confers a loss of function to the Braf protein as demonstrated by inability to activate downstream reporter assays, impaired kinase activity and presence in genetic diseases associated with Ras/Raf/Mek dysfunction (PMID: 26065894, PMID: 16474404, PMID: 16439621).
T488_P492del deletion gain of function - predicted BRAF T488_P492del results in the deletion of five amino acids near the alphaC-helix region of the protein kinase domain in the Braf protein from amino acids 488 to 492 (PMID: 26732095). T488_P492del results in activation of Mek in cell culture (PMID: 26996308), and similar Braf deletions are activating (PMID: 26996308, PMID: 26732095), and therefore T488_P492del is predicted to confer a gain of function to the Braf function.
H725Y missense unknown BRAF H725Y lies within the protein kinase domain of the Braf protein (UniProt.org). H725Y has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
G596V missense loss of function - predicted BRAF G596V lies within the protein kinase domain of the Braf protein (UniProt.org). G596V results in impaired Braf kinase activity and does not activate downstream MEK and ERK in cell culture (PMID: 16439621), but leads to activation of ERK in zebrafish models (PMID: 19376813), and is therefore predicted to lead to a loss of Braf protein function.
L485_P490delinsF indel gain of function - predicted BRAF L485_P490delinsF results in a deletion of six amino acids near the alphaC-helix region of the Braf protein kinase domain combined with the insertion of one new amino acid in the same location (PMID: 26732095). L485_P490delinsF is associated with increased Erk phosphorylation in human tumor samples (PMID: 29544532), and increased activation of MEK/ERK signaling in combination with L485_P490delinsY in cultured cells (PMID: 26732095), and therefore is predicted to confer a gain of function to the Braf protein.
D594N missense loss of function - predicted BRAF D594N lies within the protein kinase domain of the Braf protein (UniProt.org). D594N results in impaired Braf kinase activity, but leads to activation of Erk signaling through CRAF in cell culture (PMID: 28783719), and demonstrates decreased transforming ability compared to wild-type Braf in one of two cell lines in culture (PMID: 29533785), and therefore is predicted to confer a loss of function to the Braf protein.
V226L missense unknown BRAF V226L lies within the Ras-binding domain of the Braf protein (UniProt.org). V226L has not been characterized in the scientific literature and therefore, its effect on Braf protein is unknown (PubMed, Apr 2018).
V471F missense loss of function BRAF V471F lies within the protein kinase domain of the Braf protein (UniProt.org). V471F results in a loss of Braf kinase activity, however, results in dimerization-dependent activation of Erk signaling and is weakly transforming in cultured cells (PMID: 25348715).
G563D missense loss of function - predicted BRAF G563D lies within the protein kinase domain of the Braf protein (UniProt.org). G563D has not been biochemically characterized, but demonstrates decreased transformation ability in cell culture compared to wild-type Braf (PMID: 29533785), and therefore is predicted to confer a loss of function to the Braf protein.
D587A missense unknown BRAF D587A lies within the protein kinase domain of the Braf protein (UniProt.org). D587A has been identified in sequencing studies (PMID: 14500346), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Apr 2018).
F595L missense unknown BRAF F595L lies within the protein kinase domain of the Braf protein (UniProt.org). F595L has been demonstrated to result in intermediate Braf kinase activity and is transforming in cell culture (PMID: 15035987, PMID: 26582644, PMID: 29533785), and works cooperatively with oncogenic Ras to activate MEK/ERK signaling (PMID: 26582644), however, has also been demonstrated to have low Braf kinase activity (PMID: 28783719), and therefore its effect on Braf protein function is unknown.
Q609E missense unknown BRAF Q609E lies within the protein kinase domain of the Braf protein (UniProt.org). Q609E has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
V600Q missense unknown BRAF V600Q (previously reported as V599) lies within the activation segment of the kinase domain of the Braf protein (PMID: 15035987). V600Q has been identified in the scientific literature (PMID: 28848703), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown.
D287H missense loss of function BRAF D287H does not lie within any known functional domains of the Braf protein (UniProt.org). D287H results in impaired Braf kinase activity, but leads to Ras-dependent activation of Erk in cell culture (PMID: 26343582, PMID: 28783719).
G69S missense unknown BRAF G69S lies within the protein kinase domain of the Braf protein (UniProt.org). G69S has not been biochemically characterized, but results in increased transformation ability compared to wild-type Braf in one of two different cell lines in culture (PMID: 29533785).
Molecular Profile Protein Effect Treatment Approaches
BRAF V487_P492delinsA gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF D594H loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF G478C loss of function - predicted
BRAF T599dup gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V600R gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF S364L no effect - predicted
BRAF E648Q loss of function - predicted
BRAF A728V gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V681I no effect - predicted
BRAF R509G no effect - predicted
BRAF S602F no effect - predicted
BRAF G469S gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V600E BRAF L505H
BRAF L505H gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G596D loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF H585Y loss of function - predicted
BRAF act mut gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L64I no effect - predicted
BRAF R188T no effect - predicted
BRAF K601E gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF D594G unknown
BRAF D594G NRAS G12D
BRAF K698R no effect - predicted
BRAF V590I no effect - predicted
BRAF P731S unknown
BRAF F294L no effect - predicted
BRAF fusion unknown
BRAF V600A no effect - predicted
BRAF D594_T599dup gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V639I no effect - predicted
BRAF L711F no effect - predicted
BRAF L485_P490del gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A762E unknown
BRAF G469V gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G615R loss of function - predicted
BRAF V504I no effect - predicted
BRAF K499N unknown
BRAF L245F unknown
BRAF G466E unknown
BRAF G466E HRAS Q61K
BRAF P490_Q494del gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V600E/K PTEN loss
BRAF V600E/K gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF V600E/K PIK3CA wild-type
BRAF G596S unknown
BRAF G606A unknown
BRAF L597V gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L597V NRAS Q61K
BRAF K601T gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF S467L unknown
BRAF dec exp no effect
BRAF dec exp KRAS G12C
BRAF S637* loss of function - predicted
BRAF V471I unknown
BRAF S607F loss of function - predicted
BRAF W450* loss of function - predicted
BRAF G596C loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF H574N no effect - predicted
BRAF V600delinsYM gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF M517I loss of function - predicted
APC mut BRAF mut PIK3CA mut SMAD4 mut TP53 mut
BRAF mut + TP53 wild-type
BRAF mut KRAS mut CDKN2A mut
BRAF mut PTEN inact mut
BRAF mut RB1 loss
BRAF mut PTEN wild-type
BRAF mut NRAS wild-type
PIK3CA mut BRAF mut
BRAF mut KRAS G12V
BRAF mut PTPN11 dec exp
BRAF mut PTEN loss
BRAF mut PTEN mut
BRAF mut STAG2 dec exp
BRAF mutant unknown
BRAF mut TP53 mut
BRAF mut NRAS mut
BRAF mut PIK3CA wild-type
BRAF mut KRAS mut
BRAF T529I unknown
BRAF V600E BRAF T529I
BRAF I582M unknown
BRAF P348T no effect - predicted
BRAF L678I loss of function - predicted
BRAF L584F unknown
BRAF G606W loss of function - predicted
BRAF W604del unknown
BRAF G466A unknown
BRAF D594N BRAF G466A EGFR over exp MET over exp
BRAF P367S unknown
BRAF T241P unknown
BRAF T401I no effect - predicted
BRAF E611D unknown
BRAF V600E NRAS G12V
BRAF V600E CDKN2A mut
BRAF V600E MAP2K1 H119P
BRAF V600E KRAS A146T
BRAF V600E PIK3CA P449T TP53 R273H
BRAF V600E EGFR G465R
BRAF V600E NRAS Q61K NRAS A146T
BRAF V600E EGFR over exp
BRAF V600E KRAS A146T KRAS A146V
PIK3CA mut BRAF V600E
BRAF V600E MAP2K1 V60E
BRAF V600E MAP2K1 P124Q
BRAF V600E KRAS G13D
BRAF V600E MAP2K1 P387S NRAS Q61K
BRAF V600E KRAS G12D
BRAF V600E PIK3CA P449T
BRAF V600E PIK3CA H1047R
BRAF V600E NRAS Q61K
BRAF V600E MAP2K1 P124L
BRAF amp BRAF V600E
BRAF V600E MAP2K1 I111N
BRAF V600E KRAS amp
BRAF V600E BRAF T529M
BRAF V600E MAP2K1 I103N
BRAF V600E MAP2K1 G128V
BRAF V600E MAP2K1 E203K
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S
MAP2K1 Q56P BRAF V600E
BRAF V600E EGFR exon 19 del MET amp
BRAF V600E PTEN wild-type
BRAF V600E MAP2K1 P124S
BRAF V600E NRAS A146T
BRAF V600E ERBB2 over exp KRAS A146V
BRAF V600E NRAS A146T MAP2K1 P387S
BRAF V600E MAP2K1 C121S
BRAF V600E KRAS mutant
BRAF V600E CSF1R positive
BRAF V600E PTEN loss
BRAF V600E MAP2K1 V211D
BRAF L514V BRAF V600E
BRAF V600E MAP2K1 Q56P
BRAF V600E PIK3CA mut
BRAF V600E MAP2K1 K59del
BRAF V600E PIK3CA H1047K
BRAF V600E PIK3CA H1047R TP53 wild-type
BRAF V600E MAP2K1 K57E
BRAF V600E PTEN loss TP53 wild-type
EGFR amp EGFR S492R BRAF V600E
BRAF V600E MAP2K1 P162S
BRAF V600E BRAF T529N
BRAF V600E PTEN mut
BRAF V600E KRAS wild-type
BRAF V600E TP53 Q192K
BRAF V600E MAP2K1 L115P
BRAF V600E EGFR amp
BRAF V600E ERBB2 pos KRAS A146V
BRAF V600E gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF K601I unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF N581K loss of function - predicted
BRAF G464R gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G466R loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L514V unknown
BRAF V459L unknown
BRAF V600dup gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF W604G unknown
BRAF R444W unknown
BRAF V600L unknown BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF A762V no effect - predicted
BRAF N581D no effect - predicted
BRAF P407L no effect - predicted
APC Q1429fs BRAF N581S ERBB2 L755S
BRAF N581S unknown
BRAF H574Q gain of function
BRAF D587E unknown
BRAF I592V unknown
BRAF G258V unknown
BRAF L597P unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF R271H no effect - predicted
BRAF R603* loss of function - predicted
BRAF D594A loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF S605F unknown
BRAF G469L unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF F259L no effect - predicted
BRAF Q262R unknown
BRAF A598T loss of function - predicted
BRAF K483M unknown
BRAF N581I unknown
BRAF S419Y no effect - predicted
BRAF H269Y unknown
BRAF T470K no effect - predicted
BRAF D594Y unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF P403fs loss of function - predicted
BRAF K601del unknown
BRAF K483E unknown
BRAF V600X PTEN H93D
BRAF V600X PIK3CA H1047R PTEN Y86fs
BRAF V600X gain of function - predicted BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
AKT1 E17K BRAF V600X PTEN pos
BRAF V600X PTEN neg
PIK3CA H1047X BRAF V600X
AKT1 Q79K BRAF V600X PTEN pos
BRAF amp BRAF V600X NRAS Q61K
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R
BRAF P453T unknown
BRAF D594E loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF V600G gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF P162S no effect - predicted
BRAF L597Q gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
MP BRAF KRAS NRAS PIK3CA
BRAF wild-type KRAS G12V
BRAF wild-type NRAS mutant
BRAF wild-type NRAS wild-type
BRAF wild-type KRAS G12C
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type
BRAF wild-type NRAS Q61K
BRAF wild-type KRAS wild-type NRAS wild-type
BRAF wild-type KRAS G13D
BRAF wild-type KRAS wild-type
BRAF wild-type KIT positive
BRAF wild-type KRAS wild-type PIK3CA R88Q
BRAF wild-type no effect
BRAF wild-type KRAS G12D
NRAS BRAF wild-type
BRAF wild-type KRAS wild-type PIK3CA mutant
AKT1 E17K KRAS wild-type BRAF wild-type
BRAF wild-type KRAS Q61K
BRAF L485_Q494del gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L597S gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A712T no effect - predicted
BRAF V504_R506dup gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A320T no effect - predicted
BRAF inact mut loss of function
BRAF G464V KRAS G13D
BRAF G464V gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L597R gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A598_T599insV gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF Y472C unknown
BRAF R462K no effect - predicted
BRAF T599I gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G606E unknown
BRAF T529N unknown
BRAF F595S unknown
BRAF T488_Q493delinsK gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF L618F loss of function - predicted
BRAF G469A gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF N486_P490del gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF P676S no effect - predicted
BRAF T529M unknown
BRAF N486D unknown
BRAF R389C no effect - predicted
BRAF W619R unknown
BRAF L485_P490delinsY gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G469R gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G469R NRAS Q61K
BRAF N581T no effect - predicted
BRAF I592M unknown
BRAF L613F unknown
BRAF V600_K601delinsE gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF D380H no effect - predicted
BRAF E275K unknown
BRAF R462I unknown
BRAF H608R unknown
BRAF L485F gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G464E gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A598S unknown
BRAF G469E unknown
BRAF I463T unknown
BRAF T599_V600insEAT gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF H568D loss of function
BRAF N20T unknown
BRAF V600K NRAS Q61K
BRAF V600K MAP2K1 P124Q
BRAF V600K MAP2K1 P124L
BRAF V600K gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF G469del loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V600M gain of function - predicted BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF M53I unknown
BRAF S605G unknown
BRAF P141L no effect - predicted
BRAF T599R gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G104E no effect - predicted
BRAF T599A loss of function
BRAF Q257H unknown
BRAF G596fs loss of function - predicted
BRAF R509H loss of function
BRAF R671Q no effect - predicted
BRAF D594V loss of function
BRAF F468C gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF F247L gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF V600D PTEN loss
BRAF V600D gain of function BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF G421V no effect - predicted
BRAF P367R gain of function
BRAF D587G unknown
BRAF E228V no effect - predicted
BRAF amp no effect
BRAF K601Q gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF A598_T599insARC gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF W531C unknown
BRAF G596R loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G596R PIK3CA E545K
BRAF G596R NRAS Q61K
BRAF K205Q no effect - predicted
BRAF Y656D loss of function - predicted
BRAF N581Y unknown
BRAF R719S no effect - predicted
BRAF A598V gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF E586K gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF P341S no effect - predicted
BRAF G466V NRAS Q61K
BRAF G466V loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G466V EGFR wild-type
BRAF K499E gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF S467A gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF rearrange unknown
BRAF T599_V600insTT gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF E501K unknown
BRAF I463S gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF W604R unknown
BRAF G606V unknown
BRAF R347* loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF N49I no effect - predicted
BRAF L485Y unknown
BRAF L485W unknown
BRAF Q609H no effect - predicted
BRAF E695K unknown
BRAF Q257R gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF S605N unknown
BRAF V600fs loss of function - predicted
BRAF T599_V600insETT gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF K601N gain of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF Y538H unknown
BRAF E501G loss of function
BRAF T488_P492del gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF H725Y unknown
BRAF G596V loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G596V NRAS G13R
BRAF L485_P490delinsF gain of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF D594N loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF V226L unknown
BRAF V471F loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120
BRAF G563D loss of function - predicted
BRAF D587A unknown
BRAF F595L unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF Q609E unknown
BRAF V600Q unknown BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan)
BRAF D287H loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor
BRAF G69S unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V487_P492delinsA pancreatic cancer resistant Dabrafenib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Tafinlar (dabrafenib) (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer sensitive LY3009120 Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA were sensitive to LY3009120 in culture and in xenograft models, resulting in inhibition of tumor growth and partial tumor regression (PMID: 26732095). 26732095
BRAF V600R melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive Dabrafenib Clinical Study Actionable In a clinical case study, a melanoma patient harboring BRAF V600R treated with Tafinlar (dabrafenib) demonstrated a reduction in lesion size after 2.5 months and at 5 months, stable disease, however, after 7 months progression ensued (PMID: 27255157). 27255157
BRAF V600R melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600E BRAF L505H melanoma resistant Vemurafenib Clinical Study Actionable In a clinical case study, a melanoma patient harboring BRAF V600E treated with Zelboraf (vemurafenib) subsequently demonstrated resistance likely due to the secondary resistance mutation, BRAF L505H (PMID: 25515853). 25515853
BRAF L505H melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). 24283590
BRAF act mut melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF act mut Advanced Solid Tumor sensitive Binimetinib + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). detail...
BRAF act mut thyroid cancer sensitive Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). 23489023
BRAF act mut Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). 24422853
BRAF act mut non-small cell lung carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). 29343524
BRAF act mut colorectal cancer no benefit Venetoclax + VX-11e Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
BRAF act mut colorectal cancer predicted - sensitive VX-11e + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
BRAF act mut melanoma sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). 22084396
BRAF K601E melanoma sensitive Trametinib Phase II Actionable In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). 23248257
BRAF K601E melanoma sensitive Trametinib Clinical Study Actionable In a clinical case study, a melanoma patient with BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). 28344857
BRAF K601E Advanced Solid Tumor sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). 22798288
BRAF K601E melanoma no benefit Dabrafenib Phase I Actionable In a Phase I trial, no responses were demonstrated among three melanoma patients with non-V600 BRAF mutations, including two patients harboring BRAF K601E, following treatment with Tafinlar (dabrafenib), compared to a confirmed response rate of 50% in patients harboring BRAF V600 mutations (PMID: 22608338). 22608338
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical Actionable In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601E (PMID: 26343582). 26343582
BRAF D594G melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF D594G in culture (PMID: 28783719). 28783719
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF fusion pilocytic astrocytoma not applicable N/A Guideline Diagnostic BRAF fusions aid in the diagnosis of pilocytic astrocytoma (NCCN.org). detail...
BRAF fusion pilocytic astrocytoma not applicable N/A Guideline Prognostic BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (NCCN.org). detail...
BRAF G469V non-small cell lung carcinoma sensitive Sorafenib Clinical Study Actionable In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions and complete response in the lung metastasis following treatment with Nexavar (sorafenib) (PMID: 27388325). 27388325
BRAF G469V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469V (PMID: 26343582). 26343582
BRAF G466E melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). 27523909
BRAF G466E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466E HRAS Q61K melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). 28783719
BRAF V600E/K PTEN loss Advanced Solid Tumor predicted - sensitive PX-866 + Vemurafenib Phase I Actionable In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). 29051322
BRAF V600E/K melanoma sensitive Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). 25399551
BRAF V600E/K melanoma sensitive Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-AD) that supported FDA approval, adjuvant treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved estimated 3-year relapse-free survival rate (58% vs 39%, HR=0.47, P<0.001) and 3-year overall survival rate (86% vs 77%, HR=0.57; 95% CI, 0.42 to 0.79, P=0.0006) compared to placebo in stage III melanoma patients harboring BRAF V600E or V600K mutations (PMID: 28891408; NCT01682083). 28891408
BRAF V600E/K melanoma sensitive Vemurafenib + Cobimetinib FDA approved Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, which included patients identified to harbor BRAF V600E or BRAF V600K (PMID: 27480103; NCT01689519). 27480103
BRAF V600E/K melanoma sensitive Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
BRAF V600E/K melanoma sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292). 22805292
BRAF V600E/K melanoma sensitive Binimetinib + Encorafenib FDA approved Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453). 29573941
BRAF V600E/K melanoma sensitive Binimetinib + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable melanoma harboring BRAF V600E or V600K mutations (NCCN.org). detail...
BRAF V600E/K PIK3CA wild-type melanoma no benefit Idelalisib Preclinical Actionable In a preclinical study, Zydelig (idelalisib) did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit A66 Preclinical Actionable In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + ZSTK474 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and ZSTK474 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergitically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Vemurafenib + ZSTK474 Preclinical Actionable In a preclinical study, ZSTK474 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + Vemurafenib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive BEZ235 + Vemurafenib Preclinical Actionable In a preclinical study, BEZ235 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit TGX-221 Preclinical Actionable In a preclinical study, TGX-221 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF L597V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF L597V (PMID: 26343582). 26343582
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K non-small cell lung carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF K601T Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601T (PMID: 26343582). 26343582
BRAF dec exp KRAS G12C lung cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition and sustained inhibition of Erk signaling in lung cancer cells harboring KRAS G12C with decreased Braf expression through shRNA knockdown in culture (PMID: 27338794). 27338794
APC mut BRAF mut PIK3CA mut SMAD4 mut TP53 mut colorectal cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, a rapamycin-resistant colorectal cancer cell line harboring mutations in APC, BRAF, PIK3CA, SMAD4 and TP53 was sensitive to Sapanisertib (MLN0128) resulting in inhibition of MTORC1 signaling (PMID: 25261369). 25261369
BRAF mut + TP53 wild-type melanoma sensitive CGM097 + LGX818 Preclinical Actionable In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). detail...
BRAF mut + TP53 wild-type melanoma sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). 25567130
BRAF mut + TP53 wild-type colorectal cancer sensitive ABT-263 + CGM097 + Dabrafenib + PF-04217903 Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
BRAF mut KRAS mut CDKN2A mut triple-receptor negative breast cancer resistant Trametinib Preclinical Actionable In a preclinical study, human triple negative breast cancer cells harboring mutant BRAF, KRAS, and CDKN2A were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 Preclinical Actionable In a preclinical study, AZD6482 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + Binimetinib Preclinical Actionable In a preclinical study, GSK2636771 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 + BYL719 Preclinical Actionable In a preclinical study, combination treatment consisting of AZD6482, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive TGX-221 Preclinical Actionable In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + NVP-AEW541 Preclinical Actionable In a preclinical study, AZD6482 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Binimetinib + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive NVP-AEW541 + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma decreased response Alpelisib Preclinical Actionable In a preclincal study, melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations were less sensitive to Alpelisib (BYL719)-induced growth inhibition in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib Preclinical Actionable In a preclinical study, AZD6482 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + BYL719 Preclinical Actionable In a preclinical study, AZD6482 and Alpelisib (BYL719) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive LGX818 + unspecified IGF-1R antibody Preclinical Actionable In a preclinical study, combination treatment consists of Encorafenib (LGX818) and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib + LGX818 + BYL719 Preclinical Actionable In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + LGX818 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771, Encorafenib (LGX818), and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + LGX818 Preclinical Actionable In a preclinical study, GSK2636771 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit Alpelisib + Binimetinib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BYL719 + GSK2636771 + LGX818 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of GSK2636771, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently inhibited tumor growth in xenograft models of a human melanoma cell line harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit BYL719 + NVP-AEW541 Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BYL719 + GSK2636771 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of GSK2636771 and Alpelisib (BYL719) synergized to inhibit proliferation of human melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture, and inhibited tumor growth in xenograft models of one cell line harboring these mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib + LGX818 + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Encorafenib + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 Preclinical Actionable In a preclincal study, AZD6482 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit BYL719 + LGX818 Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and Encorafenib (LGX818) combination treatment did not enhance growth inhibition in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + NVP-AEW541 Preclinical Actionable In a preclinical study, GSK2636771 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Pictilisib Preclinical Actionable In a preclincal study, Pictilisib (GDC-0941) inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut RB1 loss melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). 27488531
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + Binimetinib Preclinical Actionable In a preclinical study, AZD6482 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit GSK2636771 + LGX818 Preclinical Actionable In a preclinical study, GSK2636771 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma sensitive E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 resulted in a cytocidal response in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture and inhibited tumor growth in cell line xenograft models (PMID: 23039341). 23039341
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + NVP-AEW541 Preclinical Actionable In a preclinical study, AZD6482 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit GSK2636771 + NVP-AEW541 Preclinical Actionable In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + LGX818 Preclinical Actionable In a preclinical study, AZD6482 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit GSK2636771 + Binimetinib Preclinical Actionable In a preclinical study, GSK2636771 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). 26169970
BRAF mut KRAS G12V melanoma resistant AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, BRAF mutant melanoma cells over-expressing KRAS G12V were resistant to Selumetinib (AZD6244) and AZ628 combination treatment in culture (PMID: 26351322). 26351322
BRAF mut PTPN11 dec exp colorectal cancer sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, knocking down of Ptpn11 expression via shRNA sensitized BRAF mutant colorectal cancer cell lines to PLX4720 in culture (PMID: 26351322). 26351322
BRAF mut PTEN loss melanoma sensitive GSK2636771 + Pembrolizumab Preclinical Actionable In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma sensitive SAR260301 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma no benefit Pembrolizumab Preclinical Actionable In a preclinical study, Keytruda (pembrolizumab) resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma sensitive SAR260301 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma sensitive SAR260301 + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 and Selumetinib (AZD6244) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma no benefit GSK2636771 Preclinical Actionable In a preclinical study, GSK2636771 resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). 26645196
BRAF mut PTEN mut melanoma predicted - sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 resulted in tumor regression in a melanoma cell line xenograft model co-harboring mutations in BRAF and PTEN (PMID: 28775144). 28775144
BRAF mut PTEN mut melanoma decreased response E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 resulted in a cytostatic response in melanoma cell lines harboring both BRAF and PTEN mutations in culture and only inhibited tumor growth at very high doses in cell line xenograft models (PMID: 23039341). 23039341
BRAF mut STAG2 dec exp melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Tafinlar (dabrafenib) in culture (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment in culture (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Zelboraf (vemurafenib) both in culture and in cell line xenograft models (PMID: 27500726). 27500726
BRAF mutant colorectal cancer sensitive Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). 28363909
BRAF mutant colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Phase Ib/II Actionable In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). detail... 28363909
BRAF mutant thyroid cancer sensitive HM95573 Preclinical - Cell culture Actionable In a preclinical study, HM95573 inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant colorectal cancer predicted - resistant SYM004 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). 29423521
BRAF mutant colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). 28611205
BRAF mutant thyroid cancer sensitive Selumetinib Phase I Actionable In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). 23406027
BRAF mutant colorectal cancer decreased response PLX4720 Preclinical - Cell culture Actionable In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). 26351322
BRAF mutant melanoma sensitive S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). 27760111
BRAF mutant pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant colorectal cancer sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant Advanced Solid Tumor sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 demonstrated safety and preliminary efficacy, resulted in partial response in 14% (4/29), and prolonged stable disease in 48% (14/29) of advanced solid tumor patients harboring mutations in KRAS, NRAS, and/or BRAF (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF mutant melanoma sensitive Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). 27488531
BRAF mutant colon cancer predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). 26140595
BRAF mutant melanoma sensitive Selumetinib Phase II Actionable In a Phase II trial in patients with advanced melanoma, 5/6 patients exhibiting a response to selumetinib had BRAF-mutant tumors (PMID: 22048237). 22048237
BRAF mutant Advanced Solid Tumor predicted - sensitive MLN2480 Preclinical - Cell culture Actionable In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). detail...
BRAF mutant colorectal cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant Advanced Solid Tumor sensitive Obatoclax Preclinical Actionable In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). 22460902
BRAF mutant Advanced Solid Tumor sensitive RAF709 Phase I Actionable In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). 29343524
BRAF mutant melanoma sensitive E6201 + LY294002 Preclinical Actionable In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). 23039341
BRAF mutant colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). 28611205
BRAF mutant stomach carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant colorectal cancer sensitive AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). 26351322
BRAF mutant non-small cell lung carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). 23039341
BRAF mutant cervix carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive Vemurafenib + Voruciclib Phase I Actionable In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). detail...
BRAF mutant colorectal cancer sensitive HM95573 Preclinical - Cell line xenograft Actionable In a preclinical study, HM95573 inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant melanoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant non-small cell lung carcinoma predicted - sensitive Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 27577079). 27577079
BRAF mutant Advanced Solid Tumor no benefit CC-90003 Phase I Actionable In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). detail...
BRAF mutant melanoma sensitive Encorafenib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant melanoma sensitive Binimetinib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant Advanced Solid Tumor predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). 26140595
BRAF mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Clinical Study Actionable In a clinical study, mutant BRAF correlated with prolonged duration on Opdivo (nivolumab) therapy compared to wild-type BRAF in non-small cell lung carcinoma patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant Advanced Solid Tumor sensitive Dabrafenib Phase I Actionable In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). 22608338
BRAF mutant Advanced Solid Tumor predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). detail...
BRAF mutant Advanced Solid Tumor decreased response XL147 Preclinical Actionable In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). 25637314
BRAF mutant pancreatic cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive S63845 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). 27760111
BRAF mutant melanoma sensitive Tubastatin A Preclinical Actionable In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). 25957812
BRAF mutant melanoma sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant melanoma sensitive MLN2480 Phase I Actionable In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). detail...
BRAF mutant melanoma predicted - sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). 28775144
BRAF mutant melanoma predicted - sensitive BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). 25873592
BRAF mutant melanoma sensitive PET-16 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). 26984758
BRAF mutant colorectal cancer predicted - sensitive Panitumumab + Trametinib + Dabrafenib Phase Ib/II Actionable In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). 27770002
BRAF mutant colorectal cancer predicted - sensitive Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). 28152546
BRAF mutant melanoma predicted - sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021). 29247021
BRAF mutant melanoma sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). 24422853
BRAF mutant melanoma sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). 28611198
BRAF mutant colon cancer predicted - sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). 27655129
BRAF mutant melanoma sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). 27307593
BRAF mutant colorectal cancer resistant Trametinib Preclinical Actionable In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mut TP53 mut colorectal cancer sensitive ABT-263 + Alpelisib + Dabrafenib + Erlotinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
BRAF mut NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). 26169970
BRAF mut NRAS mut melanoma predicted - sensitive BI-847325 Preclinical - Cell culture Actionable In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). 25873592
BRAF mut PIK3CA wild-type colorectal cancer predicted - sensitive TAK-733 Preclinical - Pdx & cell culture Actionable In a preclinical study, mutations in BRAF, KRAS, or NRAS were associated with sensitivity to TAK-733 in colorectal cancer cell lines in culture, and patient-derived xenograft models harboring KRAS or BRAF mutations with wild-type PIK3CA demonstrated a trend toward higher tumor growth inhibition following TAK-733 treatment (PMID: 26439693). 26439693
BRAF mut KRAS mut melanoma predicted - sensitive BI-847325 Preclinical - Cell culture Actionable In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to a KRAS mutation in culture (PMID: 25873592). 25873592
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive INC280 + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination of Mekinist (trametinib) and Capmatinib (INC280) induced tumor regression in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Capmatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Capmatinib (INC280) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF D594N BRAF G466A EGFR over exp MET over exp collecting duct carcinoma sensitive Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) inhibited tumor growth and reduced ERK signaling in a patient-derived xenograft (PDX) model derived from the ovarian metastasis of a patient with collecting duct carcinoma, which harbored BRAF D594N and BRAF G466A and had high levels of MET and EGFR expression (PMID: 28783719). 28783719
BRAF V600E NRAS G12V melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). 26267534
BRAF V600E NRAS G12V melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 H119P melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E treated with Selumetinib (AZD6244) in culture demonstrated resistance, which was a result of the resistance mutation, MAP2K1 H119P (PMID: 19915144). 19915144
BRAF V600E KRAS A146T colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS A146T mutation and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E PIK3CA P449T TP53 R273H colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and growth of colorectal cancer cells harboring BRAF V600E, PIK3CA P449T, and TP53 R273H in culture and in cell line xenograft models, but did not have synergistic effect on apoptosis (PMID: 26272063). 26272063
BRAF V600E EGFR G465R colorectal cancer sensitive Vemurafenib + Gefitinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Iressa (gefitinib) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Vemurafenib + Panitumumab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Panitumumab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Vectibix (panitumumab) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Erbitux (cetuximab) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquired secondary resistance mutation of EGFR G465R (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Gefitinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Iressa (gefitinib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) were resistant to Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR G465R colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired an EGFR G465R mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600E EGFR over exp colorectal cancer resistant Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, over expression of wild type EGFR in colorectal cancer cells harboring BRAF V600E resulted in sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR over exp colorectal cancer sensitive EBI-907 Preclinical - Cell culture Actionable In a preclinical study, EBI-907 inhibited growth of colorectal cancer cells harboring BRAF V600E and EGFR overexpression in culture (PMID: 26810733). 26810733
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to combination treatment consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture, likely due to the acquisition of KRAS A146V and A146T secondary resistance mutations (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V60E melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 V60E melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in cell culture (PMID: 25370473). 25370473
BRAF V600E KRAS G13D colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquisition of KRAS G13D (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G13D colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G13D mutation and subsequent resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E KRAS G12D colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Regorafenib + Cetuximab Preclinical Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). 23629727
BRAF V600E PIK3CA P449T colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). 25838391
BRAF V600E PIK3CA H1047R thyroid carcinoma resistant Everolimus Clinical Study Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to treatment with Afinitor (everolimus) (PMID: 27797976). 27797976
BRAF V600E PIK3CA H1047R thyroid carcinoma resistant Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to the combination therapy, Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 27797976). 27797976
BRAF V600E PIK3CA H1047R thyroid carcinoma sensitive Dabrafenib + Everolimus + Trametinib Clinical Study Actionable In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated tumor regression when treated with the triple combination, Tafinlar (dabrafenib), Mekinist (trametinib), and Afinitor (everolimus) (PMID: 27797976). 27797976
BRAF V600E NRAS Q61K melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). 21107323
BRAF V600E NRAS Q61K melanoma sensitive XL888 Preclinical Actionable In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). 22351686
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K lung adenocarcinoma predicted - resistant Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). 29631033
BRAF V600E MAP2K1 P124L melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 P124L melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF amp BRAF V600E lung adenocarcinoma sensitive Dabrafenib + SCH772984 + Trametinib Preclinical - Pdx Actionable In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable tumor inhibition in cell line xenograft models of BRAF V600E mutated lung adenocarcinoma cells that acquired resistance to Erk inhibitors through BRAF amplification (PMID: 28714990). 28714990
BRAF amp BRAF V600E colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF amp BRAF V600E colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification (PMID: 27312529). 27312529
BRAF amp BRAF V600E colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF amp BRAF V600E lung adenocarcinoma decreased response SCH772984 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived BRAF V600E mutant lung adenocarcinoma cells that acquired resistance to Erk inhibitor through BRAF amplification were less sensitive to SCH772984 in culture (PMID: 28714990). 28714990
BRAF V600E MAP2K1 I111N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 I111N melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E KRAS amp colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired KRAS amplification (PMID: 27312529). 27312529
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E MAP2K1 I103N melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 I103N melanoma resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 G128V melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 G128V melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 E203K melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 E203K melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 E203K melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
MAP2K1 Q56P BRAF V600E melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the B-RAF inhibitor PLX4720 in culture (PMID: 19915144). 19915144
MAP2K1 Q56P BRAF V600E melanoma sensitive Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, combined treatment with selumetinib and PLX4720 strongly suppressed the emergence of resistant MAP2K1 mutations in BRAF V600E cells in culture (PMID: 19915144). 19915144
MAP2K1 Q56P BRAF V600E melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the MEK inhibitor selumetinib (AZD6244) cell culture. 19915144
BRAF V600E EGFR exon 19 del MET amp lung adenocarcinoma resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR exon 19 deletion treated with Tagrisso (osimertinib) showed progression after 16 months and was subsequently found to have acquired BRAF V600E and MET amplification (PMID: 29596911). 29596911
BRAF V600E MAP2K1 P124S melanoma resistant Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and MAP2K1 P124S demonstrated decreased sensitivity to Selumetinib (AZD6244) compared to cells harboring BRAF V600E alone in culture (PMID: 22197931). 22197931
BRAF V600E MAP2K1 P124S melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 P124S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture (PMID: 24265153). 24265153
BRAF V600E NRAS A146T melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E ERBB2 over exp KRAS A146V stomach cancer predicted - resistant Trastuzumab Clinical Study Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified KRAS A146V and BRAF V600E in 1 patient demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma no benefit Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Zelboraf (vemurafenib)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Clinical Study Actionable In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma decreased response Selumetinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 C121S melanoma resistant Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 C121S melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 C121S melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). 21383288
BRAF V600E KRAS mutant colorectal cancer resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of BRAF V600E in KRAS-mutant colorectal cancer cells resulted in resistance to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E KRAS mutant colorectal cancer sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of KRAS-mutant melanoma cells over expressing BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E CSF1R positive melanoma sensitive Pexidartinib + Vemurafenib Preclinical Actionable In a preclinical study, a melanoma mouse model harboring BRAF V600E treated with Zelboraf (vemurafenib) demonstrated a greater drug induced sensitivity when treatment was combined with PLX3397, resulting in increased infiltration of lymphocytes via Csf1r inhibition and elevated antitumor activity (PMID: 25939769). 25939769
BRAF V600E PTEN loss melanoma sensitive GSK2636771 + unspecified PD-1 antibody Preclinical Actionable In a preclinical study, treatment with the combination of GSK2636771 and a PD-1 antibody resulted in greater tumor infiltration of T-cells and tumor growth inhibition in mouse melanoma models expressing BRAF V600E with PTEN loss compared to either agent alone (PMID: 26645196). 26645196
BRAF V600E PTEN loss melanoma resistant Everolimus Clinical Study Actionable In a clinical study, a melanoma patient harboring PTEN loss and BRAF V600E demonstrated resistance to Afinitor (everolimus) treatment, resulting in progressive disease (PMID: 20664172). 20664174 20664172
BRAF V600E PTEN loss melanoma sensitive Pictilisib + PLX4720 Preclinical Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and PTEN loss demonstrated sensitivity when treated with a combination of Pictilisib (GDC-0941) and PLX4720, resulting in decreased cell proliferation in culture (PMID: 24265153). 24265153
BRAF V600E PTEN loss melanoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600E (PMID: 25637314). 25637314
BRAF V600E PTEN loss melanoma sensitive GDC0879 + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, GDC0879 and Pictilisib (GDC-0941) synergistically inhibited survival of melanoma cell lines harboring BFAF V600E and PTEN loss in cell culture (PMID: 19276360). 19276360
BRAF V600E MAP2K1 V211D melanoma resistant CI-1040 Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by CI-1040 in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D melanoma resistant Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by Selumetinib (AZD6244) in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (Ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3290 Preclinical - Cell culture Actionable In a preclinical study, BGB3290 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3245 Preclinical - Cell culture Actionable In a preclinical study, BGB3245 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Tafinlar (dabrafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E ganglioglioma resistant Dabrafenib Clinical Study Actionable In a clinical case study, a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E progressed after initial response to Tafinlar (dabrafenib) treatment, and was found to have acquired a BRAF L514V in cis with BRAF V600E, which conferred dabrafenib resistance in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response PLX8394 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response TAK-632 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to TAK-632-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF V600E MAP2K1 Q56P melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 Q56P melanoma decreased response Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 Q56P melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). 22389471
BRAF V600E PIK3CA mut colorectal cancer sensitive ASN003 Preclinical - Cell line xenograft Actionable In a preclinical study, a colorectal cancer cell line xenograft model co-harboring BRAF V600E and a PIK3CA mutation demonstrated tumor growth inhibition when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). detail...
BRAF V600E MAP2K1 K59del melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma resistant Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E harboring MAP2K1 K59del in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 K59del melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E PIK3CA H1047K melanoma sensitive ARQ092 + Trametinib Preclinical - Pdx Actionable In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and PIK3CA H1047K was sensitive to the combination treatment of ARQ092 and Mekinist (trametinib), demonstrating a greater inhibition of tumor growth when compared to either agent alone (PMID: 26469692). 26469692
BRAF V600E PIK3CA H1047R TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture (PMID: 26272063). 26272063
BRAF V600E MAP2K1 K57E melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 K57E in a melanoma cell line harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600E PTEN loss TP53 wild-type colorectal cancer sensitive MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). 26272063
EGFR amp EGFR S492R BRAF V600E colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, a colorectal cancer patient harboring EGFR amplification, BRAF V600E, and EGFR S492R demonstrated resistance to Erbitux (cetuximab) (PMID: 22270724). 22270724
BRAF V600E MAP2K1 P162S melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P162S melanoma sensitive Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P162S melanoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). 24265154
BRAF V600E BRAF T529N Advanced Solid Tumor conflicting Sorafenib Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to Nexavar (sorafenib)-mediated inhibition of Erk phosphorylation but were equally as sensitive to Nexavar (sorafenib)-mediated growth inhibition as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to SB590885 in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor resistant RAF265 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to RAF265 in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to PLX4720 in culture (PMID: 20538618). 20538618
BRAF V600E PTEN mut melanoma sensitive ASN003 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line xenograft model co-harboring BRAF V600E and a PTEN mutation demonstrated tumor growth inhibition when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). detail...
BRAF V600E KRAS wild-type colorectal cancer no benefit Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment did not result in enhanced antitumor activity compared to Ibrance (palbociclib) alone in PDX models of KRAS wild-type colorectal cancer harboring BRAF V600E (PMID: 26369631). 26369631
BRAF V600E TP53 Q192K colon cancer sensitive Vemurafenib + Panitumumab Clinical Study Actionable In a clinical study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 28514312). 28514312
BRAF V600E MAP2K1 L115P melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P melanoma resistant PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 L115P melanoma resistant Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 L115P colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Selumetinib (AZD6244) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer sensitive Cetuximab + Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Selumetinib (AZD6244), and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquired EGFR amplification (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E EGFR amp colorectal cancer resistant Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired EGFR amplification and subsequent resistance to Selumetinib (AZD6244) and Zelboraf (vemurafenib) combination treatment were resistant to Erbitux (cetuximab) in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma decreased response Dabrafenib + SCH772984 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable inhibition of Erk signaling and proliferation of melanoma cells overexpressing BRAF V600E in culture (PMID: 28714990). 28714990
BRAF V600E colorectal cancer sensitive Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) decreased tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 23942066). 23942066
BRAF V600E glioblastoma multiforme sensitive BI2536 + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). 26573800
BRAF V600E colorectal cancer sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive SBI-755199 Preclinical Actionable In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). 26603897
BRAF V600E melanoma sensitive SB590885 Preclinical - Cell culture Actionable In a preclinical study, SB590885 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E lung carcinoma resistant Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) failed to induce apoptosis in lung carcinoma cells expressing BRAF V600E (PMID: 22649091). 22649091
BRAF V600E non-small cell lung carcinoma sensitive Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E thyroid cancer sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 thyroid cancer patient harboring BRAF V600E, who remained on treatment for over 481 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF V600E glioblastoma multiforme sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma sensitive Cediranib + Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, PLX4720, Cediranib (AZD-2171) and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E colorectal cancer sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E colorectal cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). 24885690
BRAF V600E colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive PLX4720 + Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). 27924459
BRAF V600E colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). 25309914
BRAF V600E melanoma sensitive BI 882370 + Trametinib Preclinical Actionable In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). 26916115
BRAF V600E pilocytic astrocytoma sensitive Dabrafenib Clinical Study Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in a near complete response and resolution of leptomeningeal dissemination in a patient with pilocytic astrocytoma harboring BRAF V600E (PMID: 28784858). 28784858
BRAF V600E colorectal cancer sensitive BI 882370 + Afatinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Gilotrif (afatinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). 26916115
BRAF V600E colorectal cancer resistant SHP099 Preclinical - Cell culture Actionable In a preclincial study, colorectal cancer cell lines harboring BRAF V600E demonstrated resistance to SHP099 in culture (PMID: 27362227). 27362227
BRAF V600E thyroid cancer decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, thyroid cancer cells harboring BRAF V600E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF V600E colon cancer sensitive PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). 16273091
BRAF V600E melanoma sensitive SCH772984 Preclinical Actionable In a preclinical study, SCH772984 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E melanoma sensitive DETD-35 Preclinical - Cell line xenograft Actionable In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). 27048951
BRAF V600E colon adenocarcinoma not applicable N/A Phase III Emerging In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). 26768652
BRAF V600E colorectal cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E colorectal cancer sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 25500121, PMID: 15294323). 25500121 15294323
BRAF V600E colorectal cancer sensitive Vemurafenib + Gefitinib Preclinical Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Iressa (gefitinib) decreased the number of viable colorectal cancer cells harboring a BRAF V600E mutation in cell culture (PMID: 22448344). 22448344
BRAF V600E colon cancer sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E colorectal cancer sensitive Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive EBI-907 Preclinical - Cell line xenograft Actionable In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). 26810733
BRAF V600E colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colon cancer predicted - sensitive Cetuxmab + Sorafenib Clinical Study Actionable In a clinical case report, a patient with metastatic colon cancer harboring BRAF V600E demonstrated a mixed radiographic response, with slight progression in some locations, however, response or stable disease for 7 months in other locations following treatment with the combination of Nexavar (sorafenib) and Erbitux (cetuximab) (PMID: 23792568). 23792568
BRAF V600E melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell lines harboring BRAF V600E mutation in culture (PMID: 24448821). 24448821
BRAF V600E colorectal cancer sensitive BGB-283 + Cetuximab Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 26208524). 26208524
BRAF V600E colorectal cancer predicted - sensitive Binimetinib + Cetuximab + Encorafenib Phase III Actionable In a Phase III (BEACON CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment resulted in an objective response rate of 48% (14/29, 3 complete responses), and stable disease in 52% (15/29) of patients with BRAF V600E metastatic colorectal cancer, with a median progression-free survival of 8.0 months (Annals of Oncology, Volume 29, Issue suppl_5; NCT02928224). detail...
BRAF V600E melanoma sensitive Encorafenib Preclinical - Cell line xenograft Actionable In preclinical studies, Encorafenib (LGX818) treatment of human melanoma xenograft models with BRAF V600E significantly decreased Mek activation and resulted in tumor regression (Cancer Res: 72(8) Suppl 1, Abstract #3790). detail...
BRAF V600E colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 demonstrated modest efficacy in patient-derived xenograft models of colorectal cancer harboring BRAF V600E, resulted in tumor growth inhibition or regression, but relapse upon discontinuation of treatment (PMID: 28611205). 28611205
BRAF V600E rectum cancer sensitive Vemurafenib + Panitumumab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Vectibix (panitumumab), and Irinotecan combination therapy is included in guidelines for advanced or metastatic rectum cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E melanoma sensitive PD-0325901 + Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in significant tumor regression in melanoma cell line xenograft models harboring BRAF V600E and demonstrated a 56% (5/9) complete response rate (PMID: 27488531). 27488531
BRAF V600E thyroid cancer sensitive Trametinib + Dabrafenib Clinical Study Actionable In a clinical case report, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). 27697975
BRAF V600E thyroid cancer sensitive Trametinib + Dabrafenib FDA approved Actionable In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 69% (11/16; 1 complete response and 10 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29072975; NCT02034110). 29072975
BRAF V600E renal cell carcinoma sensitive Vemurafenib Clinical Study Actionable In a clinical case study, a patient with metastatic renal cell carcinoma harboring BRAF V600E demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26918217). 26918217
BRAF V600E melanoma sensitive BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of melanoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models of BRAF V600E-positive melanoma, including models with BRAF-inhibitor resistance (PMID: 25873592). 25873592
BRAF V600E thyroid cancer sensitive Dasatinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E colorectal cancer sensitive BGB-283 Preclinical - Pdx & cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in colorectal cancer cell lines harboring BRAF V600E in culture, and resulted in partial tumor regression in both cell line and patient-derived xenograft models (PMID: 26208524). 26208524
BRAF V600E hairy cell leukemia sensitive Vemurafenib Phase II Actionable In two Phase II clinical studies, patients with refractory hairy cell leukemia harboring BRAF V600E responded to Zelboraf (vemurafenib) with overall response rates of 96% (25/26) and 100% (24/24) as well as complete response rates of 35% (9/26) and 42% (10/24) with median follow up times of 8 and 12 weeks, respectively (PMID: 26352686). 26352686
BRAF V600E thyroid cancer sensitive Lapatinib + Vemurafenib Preclinical Actionable In a preclinical study, the combination of Tykerb (lapatinib) and Zelboraf (vemurafenib) inhibited growth of thyroid cancer cells harboring a BRAF V600E mutation in culture and in BRAF-mutant mouse models of thyroid cancer (PMID: 23365119). 23365119
BRAF V600E colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). 24422853
BRAF V600E melanoma sensitive Imatinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gleevec (imatinib) and PLX4720 enhanced antitumor efficacy of melanoma cells harboring BRAF V600E, demonstrating decreased cell survival in xenograft models, and decreased phosphorylation of Mapk1 in culture (PMID: 27924459). 27924459
BRAF V600E melanoma sensitive Refametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Refametinib (BAY86-9766) inhibited growth of melanoma cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). 19706763
BRAF V600E lung cancer sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients with lung cancer each harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E glioblastoma multiforme sensitive BI2536 Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). 26573800
BRAF V600E melanoma sensitive DEL-22379 Preclinical - Cell line xenograft Actionable In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). 26267534
BRAF V600E colorectal cancer sensitive Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive Vemurafenib + Cetuximab Clinical Study Actionable In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer (PMID: 24523613). 24523613
BRAF V600E melanoma sensitive Selumetinib Phase II Actionable In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). 22048237
BRAF V600E colorectal cancer sensitive Lapatinib + Panobinostat Preclinical Actionable In a preclinical study, Tykerb (lapatinib) and Faridak (panobinostat) worked synergistically to inhibit growth of BRAF V600E mutant colorectal cancer cells in culture (PMID: 21464044). 21464044
BRAF V600E colorectal adenocarcinoma sensitive DEL-22379 Preclinical - Pdx Actionable In a preclinical study, DEL-22379 inhibited tumor growth in a colorectal adenocarcinoma patient-derived xenograft model harboring BRAF V600E (PMID: 26267534). 26267534
BRAF V600E melanoma no benefit SHP099 Preclinical Actionable In a preclinical study, SHP099 did not inhibit proliferation or ERK activation in a melanoma cell line harboring BRAF V600E in culture (PMID: 27362227). 27362227
BRAF V600E melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E colorectal cancer sensitive Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive Erlotinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Tarceva (erlotinib) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models and culture (PMID: 27924459). 27924459
BRAF V600E melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E Advanced Solid Tumor sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E melanoma sensitive Encorafenib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928). 28351928
BRAF V600E melanoma no benefit Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Ibrance (palbociclib) in a melanoma cell line xenograft model harboring BRAF V600E resulted in no benefit, demonstrating low but continuous growth (PMID: 27488531). 27488531
BRAF V600E melanoma sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in melanoma cell lines harboring BRAF V600E in culture (PMID: 26208524). 26208524
BRAF V600E melanoma sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 of 2 melanoma patients harboring BRAF V600E, who remained on treatment for over 249 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF V600E melanoma predicted - sensitive RAF265 Phase I Actionable In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). 28719152
BRAF V600E melanoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E melanoma sensitive Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
BRAF V600E melanoma sensitive Saracatinib Preclinical Actionable In a preclinical study, saracatinib inhibited proliferation of human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). 23242808
BRAF V600E melanoma sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E non-small cell lung carcinoma sensitive Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E melanoma sensitive Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, PLX4720 and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E colon cancer sensitive Vemurafenib + Cetuximab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Erbitux (cetuximab), and Camptosar (irinotecan) combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E melanoma sensitive Vemurafenib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E neuroendocrine tumor sensitive Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). 27048246
BRAF V600E non-small cell lung carcinoma sensitive Dabrafenib Phase II Actionable In a Phase II trial, 33% (26/78) of previously treated non-small cell lung carcinoma patients harboring BRAF V600E demonstrated an overall response, which included all partial responses, when treated with Tafinlar (dabrafenib) while 67% (4/6) receiving Tafinlar (dabrafenib) as a first-line treatment achieved partial responses (PMID: 27080216; NCT01336634). 27080216
BRAF V600E non-small cell lung carcinoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E melanoma sensitive CCT196969 Preclinical - Pdx Actionable In a preclinical study, CCT196969 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). 25500121
BRAF V600E melanoma sensitive INU-152 Preclinical - Cell line xenograft Actionable In a preclinical study, INU-152 reduced MEK and ERK phosphorylation and growth of a melanona cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 28645859). 28645859
BRAF V600E Advanced Solid Tumor predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of transformed cells over expressing BRAF V600E in culture, while single agent inhibition had no effect (PMID: 26140595). 26140595
BRAF V600E melanoma sensitive RO4987655 Preclinical - Cell culture Actionable In a preclinical study, RO4987655 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). 26438159
BRAF V600E melanoma sensitive ASN003 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma xenograft model harboring BRAF V600E demonstrated tumor regression when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). detail...
BRAF V600E ganglioglioma predicted - sensitive Dabrafenib Clinical Study Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in partial response 8 weeks after therapy initiation in a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E, but disease progression occurred at 40 weeks due to acquired resistance (PMID: 29880583). 29880583
BRAF V600E melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E melanoma sensitive Dabrafenib FDA approved Actionable In a Phase III clinical trial (BREAK-3) that supported FDA approval, Tafinlar (dabrafenib) improved median progression-free survival compared to Deticene (dacarbazine) (5.1 vs 2.7 months, HR=0.3, p<0.0001) in patients with BRAF V600E positive melanoma (PMID: 22735384; NCT01227889). 22735384
BRAF V600E melanoma sensitive Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive PLX7904 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX7904 inhibited survival of colorectal cancer cells harboring BRAF V600E in culture and demonstrated anti-tumor activity in cell line xenograft models (PMID: 26466569). 26466569
BRAF V600E skin melanoma sensitive Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor Ganetespib destabilized BRAF, especially BRAF V600E, resulted in loss of cell viability in culture and antitumor effects in cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E thyroid cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive PLX4720 + TAK-632 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and TAK-632 combination treatment resulted in durable inhibition of Erk signaling and tumor growth in xenograft models of colorectal cancer cells harboring BRAF V600E (PMID: 27523909). 27523909
BRAF V600E Advanced Solid Tumor sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited viability of a variety of cancer cell lines harboring BRAF V600E in culture (PMID: 26208524). 26208524
BRAF V600E non-small cell lung carcinoma sensitive Trametinib + Dabrafenib Guideline Actionable Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations (NCCN.org). detail...
BRAF V600E non-small cell lung carcinoma sensitive Trametinib + Dabrafenib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634). 27283860 27080216 detail... 28919011
BRAF V600E melanoma sensitive PAC-1 + Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of PAC-1 to Mekinist (trametinib) and Zelboraf (vemurafenib) led to greater levels of caspase-3 activity and apoptosis in melanoma cells harboring BRAF V600E when compared to Zelboraf (vemurafenib) and Mekinist (trametinib) treatment without PAC-1 (PMID: 27297867). 27297867
BRAF V600E pleomorphic xanthoastrocytoma predicted - sensitive Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in clinical benefit lasted for 16 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). 29632053
BRAF V600E thyroid cancer predicted - sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E colorectal cancer sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). 21170960
BRAF V600E colon cancer sensitive GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). 19276360
BRAF V600E colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer no benefit Panitumumab + Trametinib Phase I Actionable In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib Clinical Study Actionable In a clinical case study, a non-small cell lung cancer patient harboring a BRAF V600E mutation had a complete response after treatment with Zelboraf (vemurafenib) (PMID: 23733758). 23733758
BRAF V600E colorectal cancer predicted - sensitive Panitumumab + Trametinib + Dabrafenib Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E melanoma sensitive Vemurafenib FDA approved Actionable In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848; NCT01006980). 28961848 21639808
BRAF V600E melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E colon carcinoma sensitive CEP-32496 Preclinical - Cell line xenograft Actionable In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human colon carcinoma cell line (PMID: 22319199). 22319199
BRAF V600E melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF V600E thyroid cancer sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive BI-69A11 Preclinical Actionable In a preclinical study, BI-69A11 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E colorectal cancer sensitive DT01 + Fluorouracil + Oxaliplatin Preclinical - Cell line xenograft Actionable In a preclinical study, DT01 increased sensitivity of human colorectal cancer (CRC) cells harboring BRAF V600E to Eloxatin (oxaliplatin) and Adrucil (5-fluorouracil), and the combination resulted in decreased liver tumor growth in CRC cell line xenograft metastasis models (PMID: 26637369). 26637369
BRAF V600E melanoma sensitive PLX4720 + Tivozanib Preclinical Actionable In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E colorectal cancer sensitive Panitumumab + Dabrafenib Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E colorectal cancer sensitive Panitumumab + Dabrafenib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). detail...
BRAF V600E melanoma sensitive Gefitinib + PLX4720 Preclinical Actionable In a preclinical study, Iressa (gefitinib) in combination with PLX4720 inhibited proliferation and tumorigenicity in human melanoma cell line harboring BRAF V600E and resistant to Braf inhibition in culture and in animal models (PMID: 23242808). 23242808
BRAF V600E melanoma sensitive Cediranib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and Cediranib (AZD-2171) worked synergistically to inhibit cell growth and induce apoptosis in PLX4720-resistant human melanoma cell lines harboring BRAF V600E in culture and to suppress tumor growth in xenograft models (PMID: 26461489). 26461489
BRAF V600E melanoma sensitive Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). 25399551
BRAF V600E melanoma sensitive Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E melanoma sensitive Trametinib + Dabrafenib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600E, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600E melanoma sensitive Trametinib + Dabrafenib Phase II Actionable In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). 28268064
BRAF V600E colorectal cancer sensitive Vemurafenib + Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) inhibited tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 28649441). 28649441
BRAF V600E melanoma sensitive Ganetespib + TAK-733 Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E melanoma sensitive PAC-1 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PAC-1 and Zelboraf (vemurafenib) resulted in a synergistic effect when treating melanoma cells harboring BRAF V600E in culture and xenograft models, demonstrating increased apoptosis and decreased tumor volume (PMID: 27297867). 27297867
BRAF V600E thyroid cancer sensitive CLM3 Preclinical Actionable In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression in thyroid cancer cells harboring BRAF V600E in culture (PMID: 24423321). 24423321
BRAF V600E Advanced Solid Tumor sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited Erk phosphorylation and cell proliferation in BRAF V600E expressing cells in culture (PMID: 20538618). 20538618
BRAF V600E colorectal cancer sensitive INU-152 Preclinical - Cell line xenograft Actionable In a preclinical study, INU-152 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture, and reduced tumor growth in BRAF V600E-mutant colorectal cancer cell line xenograft models (PMID: 28645859). 28645859
BRAF V600E melanoma sensitive Cobimetinib Phase I Actionable In a Phase I trial, Cotellic (cobimetinib) treatment resulted in a confirmed partial response in six melanoma patients harboring BRAF V600E (PMID: 27424159). 27424159
BRAF V600E glioblastoma multiforme decreased response PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). 26573800
BRAF V600E colon cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited Braf V600E in vitro and inhibited growth of human colon cancer cells harboring BRAF V600E in culture (PMID: 21325073, PMID: 24042735). 24042735 21325073
BRAF V600E ovarian cancer sensitive CI-1040 Preclinical - Cell line xenograft Actionable In a preclinical study, CI-1040 inhibited growth of a human ovarian cancer cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). 19018267
BRAF V600E melanoma sensitive CCT241161 Preclinical - Pdx Actionable In a preclinical study, CCT241161 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). 25500121
BRAF V600E melanoma sensitive S3I-201 Preclinical Actionable In a preclinical study, S3I-201 inhibited cell invasion and Stat3 signaling in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). 23242808
BRAF V600E melanoma sensitive RO5126766 Preclinical - Cell culture Actionable In a preclinical study, RO5126766 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). 26438159
BRAF V600E colorectal cancer sensitive Dabrafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation had increased sensitivity to Tafinlar (dabrafenib) in culture compared to cell lines with wild-type BRAF (PMID: 24885690). 24885690
BRAF V600E melanoma sensitive SBI-0640726 Preclinical Actionable In a preclinical study, SBI-0640726 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma sensitive DETD-35 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, DETD-35 and Zelboraf (vemurafenib) synergistically inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). 27048951
BRAF V600E colorectal cancer sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E colorectal cancer sensitive Vemurafenib + Erlotinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Tarceva (erlotinib) resulted in improved inhibition of tumor growth in BRAF V600E mutant human colon cancer cell line xenograft models compared to either drug as monotherapy (PMID: 22448344). 22448344
BRAF V600E thyroid cancer sensitive Dasatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Selumetinib (AZD6244) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive PD-0325901 Preclinical Actionable In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E melanoma sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). 26343583
BRAF V600E glioblastoma multiforme decreased response PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). 26573800
BRAF V600E colorectal cancer sensitive Vemurafenib + Panitumumab Phase I Actionable In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 25589621). 25589621
BRAF V600E non-small cell lung carcinoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive Refametinib Preclinical Actionable In a preclinical study, Refametinib (BAY86-9766) inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). 19706763