Gene Detail

Gene Symbol KRAS
Synonyms C-K-RAS | c-Ki-ras2 | CFC2 | K-Ras | K-RAS2A | K-RAS2B | K-RAS4A | K-RAS4B | KI-RAS | KRAS1 | KRAS2 | NS | NS3 | RALD | RASK2
Gene Description KRAS, KRAS proto-oncogene, GTPase, is a member of the small GTPase superfamily and a key regulator of the MAPK, PI3K/AKT/mTOR pathways (PMID: 23622131). KRAS mutations are identified in a wide range of cancers (PMID: 28666118).
Entrez Id 3845
Chromosome 12
Map Location 12p12.1
Canonical Transcript NM_033360

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
P110S missense unknown KRAS P110S does not lie within any known functional domains of the Kras protein (UniProt.org). P110S has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Q61P missense loss of function - predicted KRAS Q61P is hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61P results in increased activation of Erk signaling in an in vitro assay (PMID: 30201956) and therefore, is predicted to result in a loss of Kras protein function.
Q61K missense loss of function - predicted KRAS Q61K is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61K has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS Q61K, which results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q25H missense unknown KRAS Q25H does not lie within any known functional domains of the Kras protein (UniProt.org). Q25H has been identified in the scientific literature (PMID: 21375404), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A59G missense loss of function KRAS A59G lies within the GTP binding domain of the Kras protein (UniProt.org). A59G increases bound GTP to KRAS, activates MAPK and PI3K pathways, and induces tumor formation in in vivo models (PMID: 27147599).
T20R missense unknown KRAS T20R does not lie within any known functional domains of the Kras protein (UniProt.org). T20R has been identified in the scientific literature (PMID: 24549645), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A59T missense unknown KRAS A59T lies within a GTP binding region of the Kras protein (UniProt.org). A59T has been identified in the scientific literature (PMID: 26924569, PMID: 28404754), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Q61A missense loss of function - predicted KRAS Q61A is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61A has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS Q61A, which results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
amp none no effect KRAS amplification indicates an increased number of copies of the KRAS gene. However, the mechanism causing the increase is unspecified.
Y40A missense loss of function - predicted KRAS Y40A lies within the swtich I region of the Kras protein (PMID: 11333268). Y40A is predicted to confer a loss of function to the Kras protein as demonstrated by reduced binding to Sos, which contributes to nucleotide stabilization, however, downstream signaling effects are unknown (PMID: 11333268).
D33E missense loss of function KRAS D33E lies within one of the GTP binding sites of the Kras protein (UniProt.org). D33E increases GTP binding to KRAS (PMID: 29235861), activates MAPK and PI3K pathways, and induces tumor formation in animal models (PMID: 27147599).
G12fs frameshift loss of function - predicted KRAS G12fs results in a change in the amino acid sequence of the Kras protein beginning at aa 12 of 189, likely resulting in premature truncation of the functional protein (UniProt.org). Due the loss of several functional domains (UniProt.org), G12fs is predicted to lead to a loss of Kras function.
Q22E missense loss of function KRAS Q22E does not lie within any known functional domains of the Kras protein (UniProt.org). Q22E results in increased rate of Kras GTP/GDP exchange and decreased sensitivity of Kras to GAPs, leading to accumulation of GTP-bound RAS and downstream pathway activation in cell culture (PMID: 20949621).
A11P missense unknown KRAS A11P lies within a GTP binding region of the Kras protein (UniProt.org). A11P has been identified in sequencing studies (PMID: 20592359, PMID: 27705932), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G12N missense loss of function - predicted KRAS G12N is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12N has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12N, which results in transformation of cells in culture (PMID: 6092966).
G12E missense loss of function - predicted KRAS G12E is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12E has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12E, which results in transformation of cells in culture (PMID: 6092966).
Q61R missense loss of function - predicted KRAS Q61R is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61R has not been characterized, but can be predicted to confer a loss of function on the Kras protein based on the effects of NRAS Q61R, which results in a loss of Nras GTPase function as indicated by increased GTP-bound Nras and subsequent activation of Mapk signaling in culture (PMID: 16818621).
Y71H missense loss of function KRAS Y71H lies within the switch II region of the Kras protein (PMID: 23059812). Y71H confers a loss of function to the Kras protein as demonstrated by increased intrinsic GTPase activity, is hypothesized to lead to increased binding to Raf1, and leads to activation of modest, but sustained activation of downstream Mek and EGF-stimulated activation of Erk (PMID: 23059812).
Q61E missense loss of function - predicted KRAS Q61E is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61E has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS Q61E, which results in decreased GTPase activity (PMID: 3510078).
A146X missense unknown KRAS A146X indicates any KRAS missense mutation that results in the replacement of the alanine (A) at amino acid 146 by a different amino acid.
E62K missense loss of function - predicted KRAS E62K does not lie within any known functional domains of the Kras protein (UniProt.org). E62K is predicted to confer a loss of function on the Kras protein as demonstrated by the ability to induce tumor formation in in vivo models, but at a later time point than other activating KRAS mutations (PMID: 27147599).
F28L missense loss of function KRAS F28L lies within the switch II region of the Kras protein (PMID: 20949621). F28L confers a loss of function to the Kras protein as demonstrated by increased bound GTP due to increased nucleotide exchange and not loss of intrinsic GTPase activity, leading to cellular transformation (PMID: 20949621, PMID: 1894650).
G15X missense unknown KRAS G15X indicates any KRAS missense mutation that results in the replacement of the glycine (G) at amino acid 15 by a different amino acid.
G12dup insertion unknown KRAS G12dup (also referred to as G12_G13insG) indicates the insertion of the duplicate amino acid, glycine (G)-12, in a GTP binding region of the Kras protein (UniProt.org). G12dup (G12_G13insG) has been identified in the scientific literature (PMID: 24594115, PMID: 16826224), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
T58I missense loss of function KRAS T58I lies within the GTP-binding pocket of the Kras protein (PMID: 20617134). T58I results in decreased Kras GTPase activity, increased phosphorylation of Mek and Akt, and is transforming in cell culture (PMID: 16474405).
A146V missense loss of function KRAS A146V is an exon four mutation that does not lie within any known functional domains of the Kras protein (UniProt.org). A146V may reduce GTPase activity of Kras, leading to increased downstream pathway activation (PMID: 20570890), and A146V increases cell proliferation and cell viability as compared to wild-type Kras, in two different cell lines (PMID: 29533785).
V160A missense unknown KRAS V160A does not lie within any known functional domains of the Kras protein (UniProt.org). V160A has been identified in sequencing studies (PMID: 24549645), but has not been biochemically characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
R164* nonsense unknown KRAS R164* results in a premature truncation of the Kras protein at amino acid 164 of 189 (UniProt.org). R164* has been identified in sequencing studies (PMID: 24200637), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G12I missense loss of function - predicted KRAS G12I is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12I has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12I, which results in transformation of cells in culture (PMID: 6092966).
G12X missense unknown KRAS G12X indicates any amino acid change at codon 12 of the Kras protein. KRAS codon 12 variants are hotspot mutations that often interfere with Ras GTPase activity, resulting in downstream pathway activation (PMID: 28666118, PMID: 22589270).
Y64H missense unknown KRAS Y64H lies within the G-domain of the Kras protein (PMID: 26080442). Y64H has been identified in sequencing studies (PMID: 23456389), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
exon2 unknown unknown KRAS exon 2 indicates an unspecified mutation has occurred in exon 2 of the KRAS gene.
G12Y missense loss of function - predicted KRAS G12Y is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12Y has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12Y, which results in transformation of cells in culture (PMID: 6092966).
Y32S missense loss of function - predicted KRAS Y32S lies within the switch I region of the Kras protein (PMID: 11333268). Y32S is predicted to confer a loss of function to the Kras protein as demonstrated by reduced binding to Sos, which contributes to nucleotide stabilization, however, downstream signaling effects are unknown (PMID: 11333268).
Y64D missense unknown KRAS Y64D lies within the G-domain of the Kras protein (PMID: 26080442). Y64D has been identified in sequencing studies (PMID: 27705932, PMID: 26220040), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G12S missense loss of function KRAS G12S is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12S results in decreased Kras GTP-GDP exchange rate and leads to increased Ras-GTP and activation of downstream signaling in cell culture (PMID: 23455880, PMID: 28484014, PMID: 26184075).
wild-type none no effect Wild-type KRAS indicates that no mutation has been detected within the KRAS gene.
R135T missense unknown KRAS R135T does not lie within any known functional domains of the Kras protein (UniProt.org). R135T has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
R68S missense unknown KRAS R68S does not lie within any known functional domains of the Kras protein (UniProt.org). R68S has been identified in sequencing studies (PMID: 28356789, PMID: 24806883), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Q22K missense loss of function KRAS Q22K does not lie within any known functional domain of the Kras protein (UniProt.org). Q22K decreases Kras GTPase activity, resulting in increased Ras-GTP and transformation of cultured cells (PMID: 11095964, PMID: 20570890).
K88* nonsense loss of function - predicted KRAS K88* results in a premature truncation of the Kras protein at amino acid 88 of 189 (UniProt.org). Due to the the loss of the GTP binding domain (UniProt.org), K88* is predicted to result in a loss of Kras protein function.
G13R missense unknown KRAS G13R is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G13R has been identified in the scientific literature (PMID: 22773565, PMID: 23196793, PMID: 22753589), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
C118S missense loss of function KRAS C118S lies within one of the GTP binding sites of the Kras protein (UniProt.org). C118S confers a loss of function to the Kras protein as demonstrated by reduced Erk phosphorylation and decreased tumorigenesis in knock-in mice harboring C118S in the murine Kras ortholog (PMID: 25394415).
Q22R missense loss of function KRAS Q22R does not lie within any known functional domains of the Kras protein (UniProt.org). Q22R results in decreased sensitivity of Kras to GAPs and increased stimulus-dependent activation of downstream signaling in cell culture (PMID: 20949621).
act mut unknown gain of function KRAS act mut indicates that this variant results in a gain of function in the Kras protein. However, the specific amino acid change has not been identified.
G12A missense loss of function KRAS G12A is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12A results in decreased Kras GTPase activity and increased activation of downstream signaling in cell culture (PMID: 23455880, PMID: 26037647).
G12V missense loss of function KRAS G12V is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12V results in decreased Kras GTPase activity and increased activation of downstream signaling in cell culture, and leads to increased tumor growth in mouse models (PMID: 23455880, PMID: 26037647, PMID: 24642870) and is transforming in cell culture (PMID: 29533785).
exon3 unknown unknown KRAS exon 3 indicates an unspecified mutation has occurred in exon 3 of the KRAS gene.
A11_G12insGA insertion loss of function KRAS A11_G12insGA results in the insertion of two amino acids in the GTP binding domain of the Kras protein between amino acids 11 and 12 (UniProt.org). A11_G12insGA reduces Kras GTPase activity, leads to increased activation of downstream Erk signaling, and promotes transformation in cultured cells (PMID: 24642870).
E31K missense no effect - predicted KRAS E31K lies within a GTP nucleotide binding region of the Kras protein (UniProt.org). E31K results in GTP activity similar to wild-type Kras (PMID: 20570890) and therefore, is predicted to have no effect on Kras protein function.
exon4 unknown unknown KRAS exon 4 indicates an unspecified mutation has occurred in exon 4 of the KRAS gene.
S17T missense unknown KRAS S17T lies within a GTP binding region of the Kras protein (UniProt.org). S17T has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
K147E missense loss of function KRAS K147E does not lie within any known functional domains of the Kras protein (UniProt.org). K147E confers a loss of function to the Kras protein as demonstrated by increased bound GTP due to increased nucleotide exchange and not loss of intrinsic activity, and activation of downstream Erk and Mek signaling (PMID: 23059812).
L159fs frameshift unknown KRAS L159fs results in a change in the amino acid sequence of the Kras protein beginning at aa 159 of 189, likely resulting in premature truncation of the functional protein (UniProt.org). L159fs has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Y64N missense unknown KRAS Y64N lies within the G-domain of the Kras protein (PMID: 26080442). Y64N has been identified in sequencing studies (PMID: 26090869), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A146T missense loss of function KRAS A146T is an exon four mutation that does not lie within any known functional domains of the Kras protein (UniProt.org). A146T decreases Kras GTPase activity, increases phosphorylation of Mek and Erk, and is transforming in cell culture and xenografts (PMID: 19075190, PMID: 20570890).
N116H missense loss of function - predicted KRAS N116H does not lie within any known functional domains of the Kras protein (UniProt.org). N116H results in increased nucleotide exchange and interferes with drug inhibition of KRAS G12C, and therefore, is predicted to result in a loss of Kras protein function (PMID: 26841430).
I36M missense unknown KRAS I36M lies within the switch I domain of the Kras protein (PMID: 17875937). I36M has been identified in sequencing studies (PMID: 27288520), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
positive unknown unknown KRAS positive indicates the presence of the KRAS gene, mRNA, and/or protein.
G13A missense unknown KRAS G13A is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G13A has been identified in the scientific literature (PMID: 16256179), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
I93F missense unknown KRAS I93F does not lie within any known functional domains of the Kras protein (UniProt.org). I93F has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G13C missense loss of function KRAS G13C is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G13C results in decreased Kras GTPase activity, as indicated by increased Ras-GTP, and leads to activation of downstream signaling in cell culture (PMID: 25705018, PMID: 21079152).
G12C missense loss of function KRAS G12C is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12C results in decreased Kras GTPase activity and activation of downstream signaling in cell culture and mouse models (PMID: 26037647 PMID: 16051643, PMID: 23455880).
G12_G13insA insertion unknown KRAS G12_G13insA results in the insertion of an alanine (A) in a GTP binding region of the Kras protein between amino acids 12 and 13 (UniProt.org). G12_G13A has been identified in sequencing studies (PMID: 21680795), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
L23R missense unknown KRAS L23R does not lie within any known functional domains of the Kras protein (UniProt.org). L23R has been identified in sequencing studies (PMID: 27416986, PMID: 21680795), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
K117X missense unknown KRAS K117X indicates any KRAS missense mutation that results in replacement of the lysine (K) at amino acid 117 by a different amino acid.
Q22* nonsense loss of function - predicted KRAS Q22* results in a premature truncation of the Kras protein at amino acid 22 of 189 (UniProt.org). Due to the loss of several functional domains (UniProt.org), Q22* is predicted to lead to a loss of Kras protein function.
G12F missense loss of function KRAS G12F is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12F results in decreased Kras GTPase activity and activation of downstream Mapk signaling (PMID: 11668624).
P110H missense unknown KRAS P110H does not lie within any known functional domains of the Kras protein (UniProt.org). P110H has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A146G missense unknown KRAS A146G does not lie within any known functional domains of the Kras protein (UniProt.org). A146G has been identified in sequencing studies (PMID: 25886136, PMID: 25840541), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
V9I missense unknown KRAS V9I does not lie within any known functional domains of the Kras protein (UniProt.org). V9I has been identified in sequencing studies (PMID: 24944587), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G13S missense unknown KRAS G13S is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G13S has been identified in the scientific literature (PMID: 15542810, PMID: 25415430), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
R68M missense unknown KRAS R68M does not lie within any known functional domains of the Kras protein (UniProt.org). R68M has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
D92Y missense unknown KRAS D92Y does not lie within any known functional domains of the Kras protein (UniProt.org). D92Y has been identified in sequencing studies (PMID: 12438234), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
E63K missense loss of function - predicted KRAS E63K does not lie within any known functional domains of the Kras protein (UniProt.org). E63K has not been characterized, however this evolutionarily conserved site in all Ras isoforms results in a loss of intrinsic Hras GTPase activity (PMID: 17412879, PMID: 1362901) and therefore, it is predicted to lead to a loss of Kras protein function.
G60E missense unknown KRAS G60E lies within a GTP binding region of the Kras protein (UniProt.org). G60E has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Aug 2018).
Q61X missense loss of function KRAS Q61X indicates any amino acid change at codon 61 of the Kras protein. KRAS codon 61 variants often interfere with Ras GTPase activity, resulting in downstream pathway activation (PMID: 28666118, PMID: 22589270, PMID: 26902995).
R97I missense unknown KRAS R97I does not lie within any known functional domains of the Kras protein (UniProt.org). R97I has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
P140H missense unknown KRAS P140H does not lie within any known functional domains of the Kras protein (UniProt.org). P140H has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
K5N missense loss of function KRAS K5N lies at the N-terminus of the Kras protein (PMID: 20949621). K5N results in decreased Kras nucleotide affinity and increased serum-dependent Mapk phosphorylation in cell culture (PMID: 20949621).
P34R missense loss of function KRAS P34R lies within the effector motif of the Kras protein (UniProt.org). P34R results in decreased sensitivity of the Kras protein to GAPs, resulting in accumulation of Ras-GTP and increased MEK and ERK phosphorylation in culture (PMID: 17875937).
Q61L missense loss of function - predicted KRAS Q61L is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61L results in increased activation of ERK and is transforming in cell culture (PMID: 26854029) and therefore, is predicted to result in decreased Kras protein function.
G13X missense loss of function - predicted KRAS G13X indicates any amino acid change at codon 13 of the Kras protein. KRAS codon 13 variants are hotspot mutations that often interfere with Ras GTPase activity, resulting in downstream pathway activation (PMID: 21993244, PMID: 22589270).
P121H missense unknown KRAS P121H does not lie within any known functional domains of the Kras protein (UniProt.org). P121H has been identified in sequencing studies (PMID: 22328975), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
D154Q missense loss of function - predicted KRAS D154Q is located in the hypervariable region of the Kras protein (UniProt.org). D145Q demonstrates GTPase activity and CRAF interaction similar to wild-type Kras, however, interferes with Kras dimerization in an in-vitro assay (PMID: 29336889), and therefore is predicted to result in a loss of Kras protein function.
G13dup missense unknown KRAS G13dup (also referred to as G13_V14insG) indicates the insertion of the duplicate amino acid, glycine (G)-13, in the GTP binding region of the Kras protein (UniProt.org). G13dup (G13_V14insG) has been identified in sequencing studies (PMID: 21704278), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A146P missense unknown KRAS A146P is an exon four mutation that does not lie within any known functional domains of the Kras protein (UniProt.org). A146P has been identified in the scientific literature (PMID: 28866095, PMID: 29296181), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A18V missense unknown KRAS A18V lies within a GTP binding region of the Kras protein (UniProt.org). A18V has been identified in sequencing studies (PMID: 24811063), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
V14I missense loss of function KRAS V14I lies within a GTP binding region of the Kras protein (UniProt.org). V14I results in decreased Kras GTPase activity and increased activation of downstream signaling in cell culture (PMID: 19075190, PMID: 20949621).
G12R missense loss of function KRAS G12R is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12R results in decreased Kras GTPase activity and increased activation of downstream signaling in cell culture (PMID: 23455880, PMID: 26037647).
A59S missense unknown KRAS A59S lies within a GTP binding region of the Kras protein (UniProt.org). A59S has been identified in sequencing studies (PMID: 23125007), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
N116S missense loss of function KRAS N116S lies within a GTP binding region of the Kras protein (UniProt.org). N116S results in alteration of Kras GDP-GTP exchange, and leads to increased Ras-GTP and ERK activation in cell culture (PMID: 22302539).
A11T missense unknown KRAS A11T lies within a GTP binding region of the Kras protein (UniProt.org). A11T has been identified in sequencing studies (PMID: 27888800), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G138V missense unknown KRAS G138V does not lie within any known functional domains of the Kras protein (UniProt.org). G138V has been identified in sequencing studies (PMID: 22460905), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
D57N missense unknown KRAS D57N lies in a conserved motif within the switch 2 region of the Kras protein (PMID: 15878843). D57N has been identified in the scientific literature (PMID: 23468066, PMID: 28380452), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G12W missense loss of function - predicted KRAS G12W is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12W has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12W, which results in transformation of cells in culture (PMID: 6092966).
G60D missense unknown KRAS G60D lies within the switch II region of the Kras protein (PMID: 20617134). G60D has been identified in the scientific literature (PMID: 25303977, PMID: 21632860), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G13D missense loss of function KRAS G13D is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G13D results in increased Kras GTP/GDP exchange and decreased Kras GTPase activity, and leads to increased activation of downstream signaling in cell culture (PMID: 23455880, PMID: 26037647).
G60R missense loss of function KRAS G60R lies within a GTP-binding region of the Kras protein (UniProt.org). G60R results in decreased Kras GTPase activity, leading to accumulation of GTP-bound Kras, but reduces Kras binding affinity for effectors, dampening pathway activation in cell culture (PMID: 20949621).
K5E missense unknown KRAS K5E does not lie within any known functional domain of the Kras protein (UniProt.org). K5E has been identified as a germline mutation in RAS syndromes (PMID: 23123965, PMID: 17704260), but has not been biochemically characterized, and therefore its effect on Kras protein function is unknown (PubMed, Sep 2018).
A11V missense unknown KRAS A11V lies within a GTP binding region of the Kras protein (UniProt.org). A11V has been identified in sequencing studies (PMID: 28031051, PMID: 27888800), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
L19F missense loss of function KRAS L19F does not lie within any known functional domain of the Kras protein (UniProt.org). L19F inhibits GTPase activity of Kras leading to increased activation of downstream signaling pathways (PMID: 17150185).
R73M missense unknown KRAS R73M does not lie within any known functional domains of the Kras protein (UniProt.org). R73M has been identified in sequencing studies (PMID: 23817572), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
E98* nonsense loss of function - predicted KRAS E98* results in the premature truncation of the Kras protein at amino acid 98 of 189 (UniProt.org). Due to the the loss of the GTP binding domain (UniProt.org), E98* is predicted to confer loss of function to the Kras protein (PMID: 20570890).
E76fs frameshift loss of function - predicted KRAS E76fs results in a change in the amino acid sequence of the Kras protein beginning at aa 76 of 189, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of a GTP binding site (UniProt.org), E76fs is predicted to lead to a loss of Kras protein function.
Q61H missense loss of function KRAS Q61H is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). Q61H results in decreased GTPase activity in the Kras protein, increased downstream signaling, and transformation of cultured cells (PMID: 20147967).
mutant unknown unknown KRAS mutant indicates an unspecified mutation in the KRAS gene.
G12L missense loss of function - predicted KRAS G12L is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G12L has not been characterized, but can be predicted to confer a loss of function on Kras protein based on the effects of HRAS G12L, which results in transformation of cells in culture (PMID: 6092966).
A59E missense unknown KRAS A59E lies within a GTP binding region of the Kras protein (UniProt.org). A59E has been identified in sequencing studies (PMID: 22931052), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
D119N missense unknown KRAS D119N lies within the GTP binding region of the Kras protein (UniProt.org). D119N, at high concentrations, results in increased binding of GTP, independent of the nucleotide exchange factor, leading to activation of Kras; however, also acts as a dominant-negative when combined with a second Kras mutation, leading to growth inhibition of cell differentiation in culture (PMID: 10454576).
G12D missense loss of function KRAS G12D is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G12D results in decreased Kras GTPase activity and increased activation of downstream signaling, promotes tumor formation in mouse models (PMID: 16474405, PMID: 26037647, PMID: 22871572) and is transforming in cell culture (PMID: 29533785).
loss unknown loss of function KRAS loss indicates loss of the KRAS gene, mRNA, and protein.
F156L missense loss of function KRAS F156L does not lie within any known functional domains of the Kras protein (UniProt.org). F156L results in decreased Kras GTPase activity and accumulation of GTP-bound Ras, and leads to increased activation of downstream signaling in cell culture (PMID: 20949621, PMID: 17875937).
I24N missense unknown KRAS I24N does not lie within any known functional domains of the Kras protein (UniProt.org). I24N has been identified in the scientific literature (PMID: 28088512, PMID: 29233960), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
T74P missense loss of function KRAS T74P does not lie within any known functional domains of the Kras protein (UniProt.org). T74P leads to increased Ras-GTP, which may result from disruption of Kras GTPase activity, and is transforming in cell culture (PMID: 19075190).
D153V missense loss of function - predicted KRAS D153V (present in isoform 2b) does not lie within any known functional domains of the Kras protein (UniProt.org). D153V does not alter Kras GTPase activity, however, results in increased MEK and ERK phosphorylation (PMID: 17875937), and is predicted to interfere with Kras autoinhibition (PMID: 25941399) and therefore, is predicted to result in a loss of Kras protein function.
I36L missense unknown KRAS I36L does not lie within any known functional domains of the Kras protein (UniProt.org). I36L has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
T158A missense unknown KRAS T158A does not lie within any known functional domains of the Kras protein (UniProt.org). T158A has not been characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
R164Q missense no effect - predicted KRAS R164Q does not lie within any known functional domains of the Kras protein (UniProt.org). R164Q was not bound to GTP, similar to wild-type Kras, in a GTPase activity assay in cultured cells (PMID: 20147967) and therefore, is predicted to have no effect on Kras protein function.
A59X missense unknown KRAS A59X indicates any KRAS missense mutation that results in the replacement of the alanine (A) at amino acid 59 by a different amino acid.
G12_G13dup duplication unknown KRAS G12_G13dup (also referred to as G12_G13insAG) indicates the insertion of two duplicate amino acids, glycine (G)-12 through glycine (G)-13, in a GTP binding region of the Kras protein (UniProt.org). G12_G13dup (G12_G13insAG) has been identified in the scientific literature (PMID: 20160721), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
P34L missense loss of function KRAS P34L lies within a GTP-binding region of the Kras protein (UniProt.org). P34L results in decreased Kras GAP sensitivity, leading to accumulation of GTP-bound Kras, but reduces Kras binding affinity for effectors, dampening pathway activation in cell culture (PMID: 20949621).
V14L missense loss of function KRAS V14L lies within a GTP-binding region of the Kras protein (UniProt.org). V14L results in decreased Kras GTPase activity, and activation of downstream pathway signaling in cell culture (PMID: 16474405).
G15S missense unknown KRAS G15S lies within a GTP binding region of the Kras protein (UniProt.org). G15S has been identified in sequencing studies (PMID: 24030381), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
A18D missense unknown KRAS A18D lies within a GTP binding region of the Kras protein (UniProt.org). The functional effect of A18D is conflicting, as A18D has been reported to confer anchorage-independent growth ability on cultured cells (PMID: 19490892), and has also been reported to have no effect on intrinsic GTPase activity or anchorage-independent growth ability on cultured cells (PMID: 25705018).
K176Q missense unknown KRAS K176Q lies within the hypervariable region of the Kras protein (UniProt.org). K176Q has not been characterized in the scientific literature and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Y64A missense unknown KRAS Y64A lies within the G-domain of the Kras protein (PMID: 26080442). Y64A leads to reduced Kras GTPase activity in a KRAS G12C background (PMID: 26841430), however, has not been individually characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G13V missense unknown KRAS G13V is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org). G13V has not been characterized, but is predicted to result in decreased GTPase activity by computational modeling (PMID: 25339142).
G10dup duplication loss of function KRAS G10dup indicates the insertion of the duplicate amino acid, glycine (G)-10, in the GTP binding domain of the Kras protein (UniProt.org). G10dup reduces Kras GTPase activity, leads to increased activation of downstream Erk signaling, and promotes transformation in cultured cells (PMID: 24642870).
K117N missense loss of function KRAS K117N is an exon four mutation, which confers a loss of function to the Kras protein (PMID: 20570890). K117N decreases GTPase activity of Kras, resulting in increased Ras-GTP and increased proliferation and transformation of cultured cells (PMID: 20570890).
K147N missense unknown KRAS K147N does not lie within any known functional domains of the Kras protein (UniProt.org). K147N has been identified in sequencing studies (PMID: 23619167), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
E62G missense unknown KRAS E62G does not lie within any known functional domains of the Kras protein (UniProt.org). E62G has been identified in sequencing studies (PMID: 24798001), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
G13E missense unknown KRAS G13E is a hotspot mutation that lies within a GTP binding region of the Kras protein (UniProt.org, PMID: 23455880). G13E has been identified in the scientific literature (PMID: 19453520), but has not been biochemically characterized and therefore, its effect on Kras protein function is unknown (PubMed, Sep 2018).
Molecular Profile Protein Effect Treatment Approaches
KRAS P110S unknown
KRAS Q61P loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61K loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
BRAF wild-type KRAS Q61K
KRAS Q25H unknown
KRAS A59G loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS T20R unknown
KRAS A59T unknown
KRAS Q61A loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
ERBB2 pos KRAS amp MET N375S
FGFR1 amp KRAS amp
EGFR exon 19 del KRAS amp
ERBB2 pos KRAS amp
PIK3CA amp KRAS amp
BRAF V600E KRAS amp
KRAS amp no effect
EGFR exon 19 del EGFR T790M KRAS amp
KRAS Y40A loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS D33E loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12fs loss of function - predicted
KRAS Q22E loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS A11P unknown
KRAS G12N loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12E loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61R loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Y71H loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61E loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS A146X unknown
KRAS E62K loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS F28L loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G15X unknown
KRAS G12dup unknown
KRAS T58I loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
BRAF V600E KRAS A146T KRAS A146V
KRAS A146V loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
BRAF V600E ERBB2 pos KRAS A146V
BRAF V600E ERBB2 over exp KRAS A146V
KRAS V160A unknown
KRAS R164* unknown
KRAS G12I loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
PIK3CA mutant KRAS G12X KRAS G13X
PIK3CA E545X KRAS G12X
PIK3CA H1047X KRAS G12X
KRAS G12X unknown MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Y64H unknown
KRAS exon 2 unknown
KRAS G12Y loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Y32S loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Y64D unknown
EGFR exon 19 del KRAS G12S
KRAS G12S loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12S STK11 inact mut
EGFR loss KRAS G12S
KRAS G12S EZH2 pos
KRAS wild-type no effect
ERBB2 positive KRAS wild-type
BRAF wild-type KRAS wild-type PIK3CA R88Q
BRAF wild-type KRAS wild-type
BRAF wild-type KRAS wild-type NRAS wild-type
EGFR dec exp KRAS wild-type
BRAF wild-type KRAS wild-type PIK3CA mutant
KRAS wild-type PIK3CA H1047R
CDKN2A loss KRAS wild-type
BRAF V600E KRAS wild-type
EGFR pos KRAS wild-type
AKT1 E17K KRAS wild-type BRAF wild-type
EGFR over exp KRAS wild-type
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type
MP BRAF KRAS NRAS PIK3CA
FGFR1 dec exp KRAS wild-type
KRAS R135T unknown
KRAS R68S unknown
KRAS Q22K loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS K88* loss of function - predicted
KRAS G13R unknown
HRAS G12R KRAS G13R
KRAS C118S loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q22R loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS act mut gain of function
KRAS G12A MET amp
KRAS G12A loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12V PIK3CA wild-type
KRAS G12V PIK3CA E545K TP53 R273*
KRAS G12V PTEN K6fs
KRAS G12V PIK3CA Q546K TP53 R282W
FGFR1 amp KRAS G12V
KRAS G12V loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
PIK3CA R88Q PTEN mut KRAS G12V
KRAS G12V PIK3CA E545K TP53 R335fs
KRAS G12V MET amp
KRAS G12V TP53 del
KRAS G12V PIK3CA E545K TP53 wild-type
BRAF wild-type KRAS G12V
KRAS G12V EZH2 pos
BRAF mut KRAS G12V
EGFR L858R KRAS G12V
KRAS exon 3 unknown
KRAS A11_G12insGA loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS E31K no effect - predicted
KRAS exon 4 unknown
KRAS S17T unknown
KRAS K147E loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS L159fs unknown
KRAS Y64N unknown
KRAS A146T loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
BRAF V600E KRAS A146T
KRAS N116H loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS I36M unknown
KRAS positive unknown
KRAS G13A unknown
KRAS I93F unknown
KRAS G13C PIK3CA H1047Y PTEN G143fs PTEN K267fs
EGFR amp FGFR1 amp KRAS G13C
KRAS G13C loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12C PTPN11 P491Q
KRAS G12C PIK3CA H1047R TP53 R248W
EML4-ALK KRAS G12C
KRAS G12C loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
BRAF dec exp KRAS G12C
KRAS G12C EZH2 pos
BRAF wild-type KRAS G12C
KRAS G12_G13insA unknown
KRAS L23R unknown
KRAS K117X unknown
KRAS Q22* loss of function - predicted
KRAS G12F loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12F PIK3CA H1047R
KRAS P110H unknown
KRAS A146G unknown
KRAS V9I unknown
KRAS G13S unknown
KRAS R68M unknown
KRAS D92Y unknown
KRAS E63K loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G60E unknown
KRAS Q61X loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
PIK3CA mutant KRAS Q61X
KRAS R97I unknown
KRAS P140H unknown
KRAS K5N loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS P34R loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61L loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61L PIK3CA E542K
KRAS Q61L PIK3CA E542K TP53 T118Qfs*5
KRAS G13X loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS P121H unknown
KRAS D154Q loss of function - predicted
KRAS G13dup unknown
KRAS A146P unknown
KRAS A18V unknown
KRAS V14I loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12R loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
HRAS G13R KRAS G12R SRC T341M
EGFR L858R KRAS G12R
KRAS G12R TP53 R248L
KRAS A59S unknown
KRAS N116S loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS A11T unknown
KRAS G138V unknown
KRAS D57N unknown
KRAS G12W loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G60D unknown
KRAS G13D PIK3CA D549N PIK3CA E545K
KRAS G13D loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
ERBB2 pos KRAS G13D
BRAF wild-type KRAS G13D
KRAS G13D PIK3CA H1047R
KRAS G13D PIK3CA E545k TP53 S241F
ERBB2 over exp KRAS G13D
BRAF V600E KRAS G13D
KRAS G13D PIK3CA E545K
KRAS G13D PIK3CA H1047R TP53 wild-type
BRAF G464V KRAS G13D
KRAS G13D PIK3CA E545K PIK3CA D549N
EML4-ALK KRAS G13D
KRAS G60R loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS K5E unknown
KRAS A11V unknown
KRAS L19F loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS R73M unknown
KRAS E98* loss of function - predicted
KRAS E76fs loss of function - predicted
MAP2K1 Y134C KRAS Q61H
KRAS Q61H loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS Q61H PIK3CA E542K
KRAS Q61H PIK3CA Q546R
KRAS Q61H PIK3CA E545K
BRAF mut KRAS mut CDKN2A mut
KRAS mut STK11 mut
KRAS mut + TP53 wild-type
APC mutant KRAS mutant KDR R961W
FGFR2 dec exp KRAS mut
KRAS mut EGFR pos
KRAS mut TP53 G105C TP53 V157fs
EGFR dec exp KRAS mut
FGFR3 dec exp KRAS mut
KRAS mut PIK3CA mut
KRAS mut + GATA2 wild-type
KRAS mutant PIK3CA H1047R
KRAS mut STK11 loss TP53 loss
KRAS mutant PIK3CA wild-type
EGFR pos KRAS mut
PIK3CA mut + KRAS mut + PTEN del
BRAF V600E KRAS mutant
KRAS mut STK11 inact mut
KRAS mutant unknown
KRAS mutant TP53 mutant
FGFR1 dec exp KRAS mut
BRAF mut KRAS mut
KRAS mutant PIK3CA E545K
KRAS G12L loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS A59E unknown
KRAS D119N unknown
KRAS G12D STK11 inact mut
BRAF wild-type KRAS G12D
PIK3CA G1049R KRAS G12D PIK3CA amp
KRAS G12D TP53 S127Y
IDH2 R172K KRAS G12D
KRAS G12D PTEN dec exp TP53 R306*
APC inact mut KRAS G12D PTEN inact mut
KRAS G12D MET amp
KRAS G12D PIK3CA H1047R TP53 wild-type
KRAS G12D TP53 R175H
KRAS G12D STK11 loss
PTEN loss KRAS G12D
KRAS G12D loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G12D MET over exp
BRAF V600E KRAS G12D
KRAS G12D PTEN loss TP53 V216M
KRAS G12D PIK3CA G1049R
KRAS G12D EZH2 pos
EGFR L858R KRAS G12D
KRAS G12D PIK3CA E545K PIK3CA H1047L TP53 wild-type
KRAS G12D PIK3CA H1047R PTEN R130G
KRAS G12D PIK3CA Q546R
ATM del KRAS G12D
PTEN pos KRAS G12D
APC inact mut KRAS G12D
KRAS G12D PIK3CA E453K
KRAS G12D PIK3CA H1047R TP53 R248W
KRAS G12D PIK3CA Q546L
KRAS loss loss of function
KRAS F156L loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS I24N unknown
KRAS T74P loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS D153V loss of function - predicted MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS I36L unknown
KRAS T158A unknown
KRAS R164Q no effect - predicted
KRAS A59X unknown
KRAS G12_G13dup unknown
KRAS P34L loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS V14L loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS G15S unknown
KRAS A18D unknown
KRAS K176Q unknown
KRAS Y64A unknown
KRAS G13V unknown
KRAS G10dup loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS K117N loss of function MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PI3K Inhibitor (Pan) PIK3CA inhibitor RAS Inhibitor (Pan) AZD4785
KRAS K147N unknown
KRAS E62G unknown
KRAS G13E unknown
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS Q61K lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS Q61K mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS Q61K lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS Q61K mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS Q61K non-small cell lung carcinoma sensitive XL147 + Carboplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of XL147 and Paraplatin (carboplatin) inhibited tumor growth and angiogenesis in xenograft models of a human non-small cell lung cancer cell line harboring KRAS Q61K, with increased efficacy compared to either agent alone (PMID: 25637314). 25637314
KRAS Q61K non-small cell lung carcinoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth and vascularization in xenograft models of a human non-small cell lung cancer cell line harboring KRAS Q61K (PMID: 25637314). 25637314
KRAS Q61K non-small cell lung carcinoma sensitive BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, BI-847325 inhibited MEK phosphorylation and proliferation and disrupted cell cycle progression in a non-small cell lung cancer cell line harboring KRAS Q61K in culture, and induced tumor stasis or regression in KRAS Q61K mutant non-small cell lung cancer cell line xenograft models (PMID: 27496137). 27496137
BRAF wild-type KRAS Q61K non-small cell lung carcinoma resistant GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells harboring KRAS Q61K in culture and in cell line xenograft models (PMID: 19276360). 19276360
KRAS A59T colon cancer sensitive Panitumumab + FOLFIRI Clinical Study Actionable In a clinical case study, a colon cancer patient harboring KRAS A59T demonstrated sensitivity to the combination treatment of Vectibix (panitumumab) and FOLFIRI, which resulted in an objective response of a 36% decrease according to RECIST (PMID: 28404754). 28404754
FGFR1 amp KRAS amp lung cancer resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line with co-amplification of FGFR1 and KRAS demonstrated insensitivity to Erdafitinib (JNJ-42756493) in culture (PMID: 28341788). 28341788
EGFR exon 19 del KRAS amp non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion and amplified KRAS were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR exon 19 del KRAS amp non-small cell lung carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Gilotrif (afatinib) after the emergence of amplified KRAS in culture (PMID: 25870145). 25870145
PIK3CA amp KRAS amp endometrial cancer sensitive BEZ235 + PD98509 Preclinical Actionable In a preclinical study, the combination of BEZ235 and the MEK1 inhibitor PD98509 worked synergistically or additively to inhibit growth of endometrial cancer cells with amplification of PIK3CA and KRAS in culture (PMID: 22662154). 22662154
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 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 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 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 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
KRAS amp melanoma sensitive Sorafenib + Carboplatin + Paclitaxel Phase III Actionable In retrospective study of a Phase III trial, melanoma patients harboring KRAS amplification treated with a combination of Paraplatin (carboplatin), Taxol (paclitaxel), and Nexavar (sorafenib) demonstrated a greater overall survival when compared to Paraplatin (carboplatin) and Taxol (paclitaxel) without Nexavar (sorafenib) (PMID: 26307133). 26307133
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma sensitive Osimertinib + Selumetinib Preclinical Actionable In a preclinical study, the combination of Tagrisso (osimertinib) and Selumetinib increased Parp cleavage, and highly suppressed phosphorylated Erk in human non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M, and a gain in KRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Iressa (gefitinib) after the emergence of EGFR T790M and amplified KRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M and amplified KRAS were resistant to Tagrisso (osimertinib) treatment in culture (PMID: 25870145). 25870145
KRAS Q61R pancreatic ductal adenocarcinoma sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS Q61R (PMID: 30045908). 30045908
KRAS Q61R pancreatic ductal adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS Q61R demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
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 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 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 + 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 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 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
PIK3CA mutant KRAS G12X KRAS G13X colorectal cancer sensitive Temsirolimus + Bevacizumab Clinical Study Actionable In a clinical study, a colorectal cancer patient harboring a PIK3CA mutation and KRAS mutations at codons 12 and 13 demonstrated stable disease when treated with a combination of Torisel (temsirolimus) and Avastin (bevacizumab) (PMID: 21216929). 21216929
PIK3CA E545X KRAS G12X colorectal cancer sensitive Temsirolimus Clinical Study Actionable In a clinical study, two colorectal cancer patients harboring both a PIK3CA E545 and KRAS G12 mutation demonstrated stable disease when treated with Torisel (temsirolimus) (PMID: 21216929). 21216929
PIK3CA H1047X KRAS G12X colorectal cancer resistant XL147 + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, the combination of XL147 plus Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in progressive disease in a patient with colorectal cancer harboring a PIK3CA H1047 mutation and KRAS G12 mutation (PMID: 21216929). 21216929
KRAS G12X pancreatic cancer sensitive Binimetinib Preclinical Actionable In a preclinical study, pancreatic cell lines with KRAS codon 12 mutations had increased sensitivity to Binimetinib (MEK162) (PMID: 25167228). 25167228
KRAS G12X colorectal cancer resistant Panitumumab Phase III Actionable In a Phase III trial, Vectibix (panitumumab) did not demonstrate efficacy in patients with metastatic colorectal cancer harboring KRAS mutations in codons 12 or 13 (PMID: 18316791; NCT00113763). 18316791
KRAS G12X lung adenocarcinoma predicted - resistant Gefitinib Clinical Study Actionable In a clinical study, KRAS codon 12 or 13 mutations were correlated with a lack of response to Iressa (gefitinib) in patients with lung adenocarcinoma (PMID: 15696205). 15696205
KRAS G12X colorectal adenocarcinoma sensitive Oxaliplatin Preclinical Actionable In a preclinical study, sensitivity to Eloxatin (oxaliplatin) was increased in colorectal tumor cell lines carrying KRAS codon 12 or 13 mutations (PMID: 23209813). 23209813
KRAS G12X pancreatic cancer resistant PHT-427 Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring a KRAS codon 12 mutation demonstrated resistance to PHT-427, resulting in increased Akt activity (PMID: 20197390, PMID: 20418756). 20197390 20418756
KRAS G12X colorectal cancer no benefit Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer (PMID: 26341920). 26341920
KRAS G12X pancreatic cancer sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human pancreatic cancer cell line harboring a KRAS codon 12 mutation (PMID: 23934108). 23934108
KRAS G12X Advanced Solid Tumor sensitive PD-0325901 Preclinical Actionable In a preclinical study, transformed cell lines with various KRAS codon 12 mutations displayed differential inhibition by PD-0325901 (PMID: 26037647). 23934108 26037647
KRAS G12X non-small cell lung carcinoma sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human non-small cell lung cancer cell line harboring a KRAS codon 12 mutation (PMID: 23934108). 23934108
KRAS exon 2 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with KRAS exon 2 mutations (NCCN.org). detail...
KRAS exon 2 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with KRAS exon 2 mutations (NCCN.org). detail...
KRAS exon 2 colorectal cancer predicted - sensitive Irinotecan + Selumetinib Phase II Actionable In a Phase II study, Selumetinib (AZD6244), in combination with Camptosar (irinotecan), resulted in a partial response in 9.7% (3/31) and stable disease in 51.6% (16/31) of colorectal cancer patients with KRAS exon 2 mutations (PMID: 25322874). 25322874
KRAS exon 2 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 2 mutations (NCCN.org). detail...
KRAS exon 2 colorectal cancer no benefit Cetuximab + Selumetinib Phase I Actionable In a Phase I trial, the combination of Erbitux (cetuximab) and Selumetinib (AZD6244) demonstrated safety, but minimal efficacy, in patients with metastatic colorectal cancer harboring KRAS exon 2 mutations, with no responses and 36% (5/14) of patients achieving stable disease (PMID: 26666244). 26666244
KRAS exon 2 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 2 mutations (NCCN.org). detail...
EGFR exon 19 del KRAS G12S lung adenocarcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, expression of KRAS G12S in lung adenocarcinoma cells harboring EGFR exon 19 deletion resulted in resistance to Tagrisso (osimertinib) in culture, consistent with KRAS G12S identified in tumor samples of a lung adenocarcinoma patient harboring EGFR exon 19 deletion who developed resistance to Tagrisso (osimertinib) (PMID: 27252416). 27252416
KRAS G12S lung adenocarcinoma no benefit Gefitinib Preclinical - Cell culture Actionable In a preclinical study, lung adenocarcinoma cells harboring KRAS G12S were insensitive to treatment with Iressa (gefitinib) in culture, demonstrating minimal inhibition of cell growth (PMID: 29925635). 29925635
KRAS G12S colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G12S mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12S pancreatic cancer sensitive Binimetinib Preclinical Actionable In a preclinical study, pancreatic cell lines with KRAS codon 12 mutations had increased sensitivity to Binimetinib (MEK162) (PMID: 25167228). 25167228
KRAS G12S lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12S mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12S non-small cell lung carcinoma sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS G12S in culture (PMID: 23629727). 23629727
KRAS G12S lung adenocarcinoma no benefit Erlotinib Preclinical - Cell line xenograft Actionable In a preclinical study, lung adenocarcinoma cells harboring KRAS G12S were insensitive to treatment with Tarceva (erlotinib) in culture, demonstrating no change in Erk, Mek, and Akt activity and minimal inhibition of cell growth (PMID: 29925635). 29925635
KRAS G12S lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12S mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12S lung cancer decreased response Trametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring KRAS G12S demonstrated a decreased response when treated with Mekinist (trametinib) in culture (PMID: 26582713). 26582713
KRAS G12S lung cancer decreased response Refametinib Preclinical Actionable In a preclinical study, a lung adenocarcinoma cell line harboring KRAS G12S demonstrated a decreased response when treated with Refametinib (BAY86-9766) in culture (PMID: 26582713). 26582713
KRAS G12S lung cancer sensitive APS-2-79 + Binimetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and Binimetinib (MEK162) worked synergistically to decrease viability of a lung cancer cell line harboring KRAS G12S in culture (PMID: 27556948). 27556948
KRAS G12S lung cancer sensitive APS-2-79 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and PD-0325901 worked synergistically to decrease viability of a lung cancer cell line harboring KRAS G12S in culture (PMID: 27556948). 27556948
KRAS G12S lung cancer sensitive APS-2-79 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and Mekinist (trametinib) worked synergistically to decrease viability of a lung cancer cell line harboring KRAS G12S in culture (PMID: 27556948). 27556948
KRAS G12S non-small cell lung carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring KRAS G12S in culture (PMID: 21325073, PMID: 23012248). 21325073 23012248
KRAS G12S non-small cell lung carcinoma sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS G12S in culture (PMID: 23629727). 23629727
KRAS G12S lung adenocarcinoma sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, lung adenocarcinoma cells harboring KRAS G12S were sensitive to treatment with Gilotrif (afatinib), demonstrating decreased cell proliferation and reduced Erk, Mek, and Akt activity in culture, and decreased tumor growth in cell-line xenograft models (PMID: 29925635). 29925635
KRAS G12S 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 KRAS G12S in culture (PMID: 25665005). 25665005
KRAS G12S lung cancer sensitive rigosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Estybon (rigosertib) inhibited Mek/Erk signaling and tumor growth in cell line xenograft models of lung cancer harboring KRAS G12S (PMID: 27104980). 27104980
KRAS G12S lung cancer decreased response PD-0325901 Preclinical Actionable In a preclinical study, a lung cancer cell line harboring KRAS G12S demonstrated a decreased response when treated with PD-0325901 in culture (PMID: 26582713). 26582713
KRAS G12S non-small cell lung carcinoma sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS G12S in culture (PMID: 23629727). 23629727
KRAS G12S non-small cell lung carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring KRAS G12S mutation in culture (PMID: 26090892). 26090892
KRAS G12S 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 KRAS G12S in culture (PMID: 25665005). 25665005
KRAS G12S lung cancer sensitive APS-2-79 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and Selumetinib (AZD6244) worked synergistically to decrease viability of a lung cancer cell line harboring KRAS G12S in culture (PMID: 27556948). 27556948
KRAS G12S lung carcinoma sensitive AZD4785 Preclinical - Cell culture Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of lung carcinoma cells harboring KRAS G12S (PMID: 28615361). 28615361
KRAS G12S STK11 inact mut non-small cell lung carcinoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a human non-small cell lung cancer cell line harboring KRAS G12S and an STK11(LKB) inactivating mutation (PMID: 25637314). 25637314
EGFR loss KRAS G12S lung adenocarcinoma sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, EGFR-deficient lung adenocarcinoma cells harboring KRAS G12S were sensitive to treatment with Gilotrif (afatinib), demonstrating decreased cell proliferation and inhibition of Erbb2 (Her2) and Erbb3 (Her3) in culture, and blocked tumor growth in cell line xenograft models (PMID: 29925635). 29925635
EGFR loss KRAS G12S lung adenocarcinoma no benefit Gefitinib Preclinical - Cell line xenograft Actionable In a preclinical study, EGFR-deficient lung adenocarcinoma cells harboring KRAS G12S did not respond to treatment with Iressa (gefitinib) in culture and in cell line xenograft models (PMID: 29925635). 29925635
KRAS G12S EZH2 pos lung adenocarcinoma sensitive DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12S in culture (PMID: 26676756) 26676756
KRAS G12S EZH2 pos lung adenocarcinoma sensitive DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to Selumetinib (AZD6244) in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12S in culture (PMID: 26676756). 26676756
KRAS wild-type colorectal cancer sensitive Panitumumab FDA approved Actionable In a Phase III trial that supported FDA approval, Vectibix (panitumumab) demonstrated clinical efficacy only in colorectal cancer patients with wild-type KRAS, resulting in a median progression-free survival of 12.3 weeks, compared to 7.3 weeks with best supportive care (BSC), improved overall survival (HR=0.67), and a response rate of 17% (21/141) (PMID: 18316791; NCT00113763). 18316791
KRAS wild-type colorectal cancer sensitive Panitumumab Phase III Actionable In a post-hoc analysis of a Phase III trial, colorectal cancer patients with KRAS wild-type demonstrated a greater overall survival (8.1 mo) upon treatment with Vectibix (panitumumab) compared to overall survival (4.4 mo) of patients with KRAS mutations randomized to best supportive care only (PMID: 23625191; NCT00113763). 23625191
KRAS wild-type colorectal cancer sensitive Panitumumab Phase III Actionable In a Phase III trial, Vectibix (panitumumab) treatment resulted in better overall survival (HR = 0.65) compared to Erbitux (cetuximab) in colorectal cancer patients harboring KRAS with wild-type exon 2 who received prior Avastin (bevacizumab) treatment (J Clin Oncol 34, 2016 (suppl; abstr 3538); NCT01001377). detail...
KRAS wild-type colorectal adenocarcinoma no benefit Cetuximab + Dasatinib + FOLFOX Phase Ib/II Actionable In a Phase Ib/II trial, the combination of Erbitux (cetuximab), Sprycel (dasatinib), and FOLFOX demonstrated minimal clinical benefit in patients with metastatic colorectal adenocarcinoma, with an overall response rate of 20% (6/30) in the Phase Ib portion, and 13% (3/24) in KRAS codon 12/13 wild-type patients in the Phase II portion (PMID: 28280091; NCT00501410). 28280091
KRAS wild-type colorectal cancer predicted - sensitive Napabucasin + Panitumumab Phase Ib/II Actionable In a Phase Ib/II clinical trial, BBI608 and Vectibix (panitumumab) combination therapy resulted in PR in 22.2% (2/9), SD in 22.2% (2/9), and median PFS of 9 weeks in colorectal cancer patients carrying wild-type Kras naive for anti-EGFR therapy; compared to SD in 53.3% (8/15), and median PFS of 16.4 weeks in patients failed anti-EGFR treatment (J Clin Oncol 33, 2015 (suppl; abstr 3617)). detail...
KRAS wild-type colorectal cancer sensitive Rilotumumab + Panitumumab Phase Ib/II Actionable In a Phase Ib/II trial, the combination of HGF inhibitor, rilotumumab, with Vectibix (panitumumab) demonstrated efficacy in previously treated patients with wild-type KRAS metastatic colorectal cancer (PMID: 24919569). 24919569
KRAS wild-type lung cancer decreased response Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) combination treatment was less efficient at inhibiting proliferation of KRAS wild-type lung cancer cells in culture (PMID: 27338794). 27338794
KRAS wild-type pancreatic cancer predicted - sensitive Gemcitabine + Refametinib Phase Ib/II Actionable In a Phase I/II trial, Refametinib (BAY86-9766) and Gemzar (gemcitabine) combination treatment resulted in improved overall response rate, disease control rate, progression-free survival, and overall survival (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months,18.2 vs. 6.6 months, respectively) in pancreatic cancer patients without detectable KRAS mutations in circulating tumor DNA (PMID: 27975152). 27975152
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase III Actionable In a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI demonstrated a significant clinical benefit in OS, PFS, and objective response compared to FOLFIRI alone in colorectal cancer patients with RAS wild-type status (PMID: 25605843). 25605843
KRAS wild-type head and neck squamous cell carcinoma predicted - sensitive Cetuximab + lenalidomide Phase I Actionable In a Phase I trial, Erbitux (cetuximab) and Revlimid (lenalidomide) combination therapy resulted in stable disease in 67% (2/3) of KRAS wild-type head and neck squamous cell cancer patients, and induced Revlimid (lenalidomide) dose-dependent increase of antibody-dependent cellular cytotoxicity (PMID: 27458141). 27458141
KRAS wild-type non-small cell lung carcinoma sensitive Erlotinib Phase I Actionable In a Phase I trial, Tarceva (erlotinib) treatment resulted in a greater survival benefit in non-small cell lung cancer patients with wild-type KRAS compared to treatment in those patients harboring KRAS mutations (PMID: 18626007). 18626007
KRAS wild-type pancreatic cancer decreased response Aphanin Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type pancreatic cancer cells were less sensitive to Aphanin induced growth inhibition and apoptosis in culture (PMID: 27333990). 27333990
KRAS wild-type colorectal cancer no benefit SYM004 Phase II Actionable In a Phase II trial, SYM004 treatment did not improve overall survival compared to standard of care in patients with metastatic colorectal cancer harboring no KRAS exon 2 mutations, and acquired resistance to anti-EGFR therapy (PMID: 29423521). 29423521
KRAS wild-type colorectal cancer sensitive Bevacizumab Phase III Actionable In a Phase III trial, addition of Erbitux (cetuximab) or Avastin (bevacizumab) to chemotherapy (FOLFIRI or mFOLFOX6) resulted in similar median overall survival (30.0 vs 29.0 months, HR=0.88, p=0.08) and median progression-free survival (10.5 vs 10.6 months, HR=0.95, p?=?0.45) in KRAS wild-type colorectal cancer patients (PMID: 28632865). 28632865
KRAS wild-type colorectal cancer sensitive Bevacizumab Clinical Study Actionable In a systematic review of 2,266 colorectal cancer patients, treatment with Avastin (bevacizumab) resulted in improved objective response rate (54.8% vs 48.3%, OR=1.42, p=0.02), median progression-free survival (HR=0.85, p=0.02), and median overall survival (HR=0.65, p=0.01) in KRAS wild-type patients compared to KRAS mutant patients (PMID: 23828442). 23828442
KRAS wild-type squamous cell carcinoma no benefit Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) did not induce growth inhibition or apoptosis in a KRAS wild-type squamous cell carcinoma cell line in culture and did not inhibit tumor growth in xenograft models (PMID: 23877793). 23877793
KRAS wild-type lung carcinoma decreased response AZD4785 Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type lung carcinoma cell lines demonstrated decreased respond to AZD4785 compared to KRAS mutant cell lines in culture (PMID: 28615361). 28615361
KRAS wild-type non-small cell lung carcinoma decreased response AZD4785 Preclinical - Pdx Actionable In a preclinical study, AZD4785 inhibited Kras expression in tumors, but had no effect on tumor growth in patient-derived xenograft models of KRAS wild-type non-small cell lung carcinoma (PMID: 28615361). 28615361
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab Phase III Actionable In a Phase III trial, addition of Erbitux (cetuximab) or Avastin (bevacizumab) to chemotherapy (FOLFIRI or mFOLFOX6) resulted in similar median overall survival (30.0 vs 29.0 months, HR=0.88, p=0.08) and median progression-free survival (10.5 vs 10.6 months, HR=0.95, p=0.45) in KRAS wild-type colorectal cancer patients (PMID: 28632865). 28632865
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab Clinical Study Actionable In a clinical study, KRAS wild-type colorectal cancer patients demonstrated a greater response to Erbitux (cetuximab) treatment compared to KRAS mutant colorectal cancer patients, including an objective response of 41% (27/66) vs 0% (0/42), a median overall survival of 43 weeks vs 27.3 weeks, and an overall survival of 74.9 weeks vs 30.6 weeks, respectively (PMID: 17998284). 17998284
KRAS wild-type colorectal cancer sensitive Panitumumab + cabozantinib Phase Ib/II Actionable In a Phase Ib trial, Cometriq (cabozantinib) and Vectibix (panitumumab) combination treatment resulted in a median progression free survival of 3.7 months, median overall survival of 7.5 months, and partial response in 14% (2/14) of KRAS wild-type colorectal patients (J Clin Oncol 34, 2016 (suppl; abstr 3548)). detail...
KRAS wild-type colorectal cancer predicted - sensitive Bevacizumab + Capecitabine Phase III Actionable In a Phase III trial, Avastin (bevacizumab) and Xeloda (capecitabine) maintenance treatment resulted in better time to first progression (HR = 0.27), time to second progression (HR = 0.42) and overall survival (HR = 0.64) in KRAS wild-type colorectal cancer patients compared to patients harboring KRAS mutations (HR = 0.40, 0.75, 1.07 respectively) (J Clin Oncol 34, 2016 (suppl; abstr 3525)). detail...
KRAS wild-type non-small cell lung carcinoma no benefit Selumetinib + Docetaxel Phase II Actionable In a Phase II trial, the combination of Selumetinib (AZD6244) and Taxotere (docetaxel) did not result in a greater clinical benefit in KRAS wild-type patients with non-small cell lung carcinoma when compared to Taxotere (docetaxel) plus placebo (PMID: 29045535; NCT01750281). 29045535
KRAS wild-type colorectal cancer sensitive Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with KRAS exon 2 wild-type colorectal cancer compared to FOLFIRI treatment alone, with an overall response rate of 35% (105/297) with the combination versus 10% (28/285) with FOLFIRI alone (PMID: 26341920). 26341920
KRAS wild-type colorectal cancer sensitive Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). 26341920
KRAS wild-type gastric adenocarcinoma sensitive GA201 Preclinical Actionable In a preclinical study, treatment with GA201 induced antibody-dependent cell-mediated cytotoxicity against KRAS wild-type gastric adenocarcinoma in culture, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
KRAS wild-type colorectal cancer predicted - sensitive Cetuximab + lenalidomide Phase I Actionable In a Phase I trial, Erbitux (cetuximab) and Revlimid (lenalidomide) combination therapy resulted in partial response in 5% (1/19) and stable disease in 32% (6/19) of KRAS wild-type colorectal cancer patients, and induced Revlimid (lenalidomide) dose-dependent increase of antibody-dependent cellular cytotoxicity (PMID: 27458141). 27458141
KRAS wild-type vaginal squamous tumor sensitive GDC-0623 Phase I Actionable In a Phase I trial, GDC-0632 treatment resulted in stable disease for more than 5 months in 13% (6/45) of patients with advanced solid tumors and 1 partial response in a squamous cell vaginal carcinoma patient carrying wild-type KRAS (Mol Cancer Ther 2013;12(11 Suppl):B75). detail...
KRAS wild-type Advanced Solid Tumor sensitive GDC-0623 Phase I Actionable In a Phase I trial, GDC-0632 treatment resulted in stable disease for more than 5 months in 13% (6/45) of patients with advanced solid tumors and 1 partial response in a squamous cell vaginal carcinoma patient carrying wild-type KRAS (Mol Cancer Ther 2013;12(11 Suppl):B75). detail...
KRAS wild-type non-small cell lung carcinoma no benefit Sorafenib Phase III Actionable In a Phase III trial, Nexavar (sorafenib) treatment in KRAS wild-type non-small cell lung carcinoma patients did not meet its primary endpoint when compared to placebo, resulting in a similar overall survival, however, did meet its secondary endpoint, showing a longer progression free survival (PMID: 26743856). 26743856
KRAS wild-type colorectal cancer decreased response AZD4785 Preclinical - Cell culture Actionable In a preclinical study, KRAS wild-type colorectal cancer cell lines demonstrated decreased respond to AZD4785 compared to KRAS mutant cell lines in culture (PMID: 28615361). 28615361
KRAS wild-type biliary tract cancer predicted - sensitive Panitumumab + Gemcitabine + Oxaliplatin Phase II Actionable In a Phase II clinical trial, a PFS difference was not observed between KRAS wild-type biliary tract cancer patients when treated with a combination of Vectibix (panitumumab), Gemzar (gemcitabine), and Eloxatin (oxaliplatin) versus Gemzar (gemcitabine) and Eloxatin (oxaliplatin) only (PMID: 26540314). 26540314
KRAS wild-type colorectal cancer predicted - sensitive Necitumumab + FOLFOX Phase II Actionable In a Phase II clinical trial, the combination of Portrazza (necitumumab) and FOLFOX in colorectal cancer patients resulted in an objective response rate (ORR) of 63.6% (28/44) in the overall intent-to-treat population, with KRAS wild-type patients achieving an ORR of 87.5% (14/16), including complete response in 25% (4/16), and partial response in 62.5% (10/16) of patients (PMID: 26766738). 26766738
ERBB2 positive KRAS wild-type colorectal cancer sensitive Trastuzumab + Lapatinib Phase II Actionable In a Phase II clinical trial, 30% (8/27) of patients with ERBB2 (HER2)-positive KRAS wild-type colorectal cancer achieved an objective response and 44% (12/27) of patients had stable disease when treated with the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 27108243). 27108243
BRAF wild-type KRAS wild-type colorectal cancer decreased response LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 demonstrated limited efficacy in BRAF and KRAS wild-type patient-derived xenograft models of colorectal cancer, resulted in a disease control rate of 3.8% (1/26) (PMID: 28611205). 28611205
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI Phase II Actionable In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Erbitux (cetuximab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 33.2 mo and response rate of 68% (40/59), however, resulted in a 10-mo PFS rate of 50.8% (30/59), which did not meet the primary endpoint of 70% (PMID: 29450468; NCT02295930). 29450468
BRAF wild-type KRAS wild-type NRAS wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFIRI + Bevacizumab Phase II Actionable In a Phase II trial (MACBETH), first-line treatment with the combination of Erbitux (cetuximab) and FOLFIRI, followed by Avastin (bevacizumab) maintenance, demonstrated activity in BRAF/KRAS/NRAS wild-type metastatic colorectal cancer patients, resulting in a median overall survival in the intent-to-treat population of 32.2 mo and response rate of 75% (43/57), however, resulted in a 10-mo PFS rate of 40.4% (23/57), which did not meet the primary endpoint of 70% (PMID: 29450468; NCT02295930). 29450468
EGFR dec exp KRAS wild-type colorectal cancer sensitive GA201 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with GA201 resulted in improved overall survival in KRAS wild-type colorectal cancer cell line xenograft models with low EGFR expression, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
EGFR dec exp KRAS wild-type colorectal cancer sensitive GA201 + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of GA201 and Camptosar (irinotecan) resulted in improved overall survival in KRAS wild-type colorectal cancer cell line xenograft models with low EGFR expression, when compared to either as a single agent (PMID: 23209031). 23209031
BRAF wild-type KRAS wild-type PIK3CA mutant colorectal cancer sensitive Cetuximab Clinical Study Actionable In a retrospective study, Erbitux (cetuximab) treatment, alone or in combination, resulted in disease regression or stable disease in 88% (7/8) KRAS/BRAF-wild type colorectal carcinoma patients harboring a PIK3CA mutation (PMID: 25714871). 25714871
KRAS wild-type PIK3CA H1047R 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 PIK3CA H1047R (PMID: 26369631). 26369631
CDKN2A loss KRAS wild-type non-small cell lung carcinoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, a squamous non-small cell lung carcinoma patient with KRAS wild-type and loss of CDKN2A demonstrated a partial response when treated with Abemaciclib (LY2835219) (PMID: 27217383). 27217383
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
EGFR pos KRAS wild-type colorectal cancer sensitive Cetuximab + FOLFIRI Phase III Actionable In a Phase III trial that supported FDA approval, the combination of Erbitux (cetuximab) and FOLFIRI resulted in a greater tumor response rate in EGFR positive, KRAS wild-type colorectal cancer patients (59% (102/172)) compared to EGFR positive, KRAS mutant colorectal cancer patients (36.2% (38/105)) (PMID: 19339720; NCT00154102). 19339720
AKT1 E17K KRAS wild-type BRAF wild-type colorectal cancer resistant Cetuximab + Irinotecan Clinical Study Actionable In a retrospective study, 100% (2/2) colorectal carcinoma patients harboring an AKT1 E17K mutation and wild-type KRAS/BRAF demonstrated resistance to Erbitux (cetuximab) in combination with Camptosar (irinotecan) (PMID: 25714871). 25714871
EGFR over exp KRAS wild-type pancreatic adenocarcinoma sensitive Trametinib + Triciribine Preclinical - Cell culture Actionable In a preclinical study, the combination of Triciribine (API-2) and Mekinist (trametinib) worked synergistically to inhibit growth of a pancreatic adenocarcinoma cell line with wild-type KRAS that demonstrated high EGFR expression and activation in culture (PMID: 28957417). 28957417
EGFR over exp KRAS wild-type pancreatic adenocarcinoma sensitive Afatinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Gilotrif (afatinib) and Mekinist (trametinib) worked synergistically to inhibit growth of a pancreatic adenocarcinoma cell line with wild-type KRAS that demonstrated high EGFR expression and activation in culture (PMID: 28957417). 28957417
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines with wild-type BRAF, KRAS, NRAS and PIK3CA were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer sensitive Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells wild-type for BRAF, KRAS, NRAS and PIK3CA in culture (PMID: 25838391). 25838391
BRAF wild-type KRAS wild-type NRAS wild-type PIK3CA wild-type colorectal cancer predicted - sensitive Cetuximab + FOLFOX Phase II Actionable In a Phase II trial, Erbitux (cetuximab) in combination with FOLFOX resulted in improved median progression-free survival (6.9 months) comparing to FOLFOX alone (5.3 months) in BRAF, KRAS, NRAS, and PIK3CA wild-type colorectal cancer patients (hazard ratio =0.56) (PMID: 27002107). 27002107
FGFR1 dec exp KRAS wild-type lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr1 through shRNA did not sensitize KRAS wild-type lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
HRAS G12R KRAS G13R thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture and in cell line xenograft models (PMID: 27222538). 27222538
HRAS G12R KRAS G13R thyroid cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture (PMID: 27222538). 27222538
HRAS G12R KRAS G13R thyroid cancer sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture (PMID: 27222538). 27222538
HRAS G12R KRAS G13R 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 thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture (PMID: 27222538). 27222538
HRAS G12R KRAS G13R 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 thyroid cancer cell lines harboring KRAS G13R and HRAS G12R in culture (PMID: 27222538). 27222538
KRAS 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
KRAS act mut 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 colorectal cancer cell lines harboring KRAS activating mutations in culture (PMID: 26351322). 26351322
KRAS act mut lung cancer predicted - sensitive Dinaciclib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring activating KRAS mutations demonstrated increased sensitivity to Dinaciclib (SCH 727965) in culture (PMID: 27550941). 27550941
KRAS 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 KRAS activating mutations (PMID: 29343524). 29343524
KRAS act mut ovarian cancer predicted - sensitive PD-0325901 + Gedatolisib Phase I Actionable In a Phase I trial, treatment with the combination of Gedatolisib (PF-05212384) and PD-0325901 resulted in an overall response rate of 11.1% (4/44) and clinical benefit rate of 16.3% (7/44) in patients with a variety of solid tumors, with responses seen in 3 patients with KRAS-mutant ovarian cancer and 1 patient with KRAS-mutant endometrial cancer (PMID: 29067643). 29067643
KRAS 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
KRAS G12A MET amp lung cancer resistant AMG 337 Preclinical - Cell culture Actionable In a preclinical study, a MET-amplified lung cancer cell line harboring KRAS G12A was not sensitive to growth inhibition by AMG 337 in culture (PMID: 27196782). 27196782
KRAS G12A MET amp lung cancer resistant SAR125844 Preclinical - Cell culture Actionable In a preclinical study, MET amplified lung cancer cells harboring KRAS G12A were insensitive to SAR125844-mediated growth inhibition in culture (PMID: 25504634). 25504634
KRAS G12A multiple myeloma sensitive Panobinostat Preclinical Actionable In a preclinical study, Farydak (panobinostat) induced caspase activation and apoptosis in a human multiple myeloma cell line harboring KRAS G12A in culture (PMD: 19490892, PMID: 22693356). 19490892 22693356
KRAS G12A multiple myeloma sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 induced caspase activation and apoptosis in a human multiple myeloma cell line harboring KRAS G12A in culture (PMID: 19490892, PMID: 22693356). 19490892 22693356
KRAS G12A colorectal cancer sensitive Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) inhibited growth of human colorectal cancer cells harboring KRAS G12A in culture (PMID: 25838391). 25838391
KRAS G12A colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring KRAS G12A were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
KRAS G12V PIK3CA wild-type colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment resulted in partial tumor regression in PDX models of PIK3CA wild-type colorectal cancer cells harboring KRAS G12V (PMID: 26369631). 26369631
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer no benefit Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment did not improve tumor growth stabilization compared to single agent in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K and TP53 R273* (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer resistant BEZ235 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R273* did not respond to BEZ235 treatment (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 R273* colorectal cancer resistant Selumetinib Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R273* did not respond to Selumetinib (AZD6244) treatment (PMID: 26272063). 26272063
KRAS G12V PTEN K6fs prostate cancer sensitive BAY1125976 Preclinical - Cell culture Actionable In a preclinical study, BAY1125976 inhibited proliferation of a prostate cancer cell line harboring KRAS G12V and PTEN K6fs*4 in culture (PMID: 27699769). 27699769
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer sensitive Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment resulted in enhanced tumor growth stabilization compared to single agent in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K and TP53 R282W (PMID: 26272063). 26272063
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer decreased response BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 delayed tumor growth of patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K, and TP53 R282W (PMID: 26272063). 26272063
KRAS G12V PIK3CA Q546K TP53 R282W colorectal cancer predicted - sensitive Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) inhibited tumor growth of patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA Q546K, and TP53 R282W (PMID: 26272063). 26272063
FGFR1 amp KRAS G12V non-small cell lung carcinoma decreased response BGJ398 Preclinical - Cell culture Actionable In a preclinical study, overexpression of KRAS G12V in FGFR1-amplified non-small cell lung carcinoma cells resulted in decreased response to BGJ398 in culture (PMID: 28630215). 28630215
FGFR1 amp KRAS G12V non-small cell lung carcinoma sensitive BGJ398 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, BGJ398 and Mekinist (trametinib) combination treatment inhibited Erk signaling, resulting in growth inhibition in FGFR1-amplified non-small cell lung carcinoma cells overexpressing KRAS G12V in culture (PMID: 28630215). 28630215
FGFR1 amp KRAS G12V lung cancer resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line harboring FGFR1 amplification and KRAS G13C demonstrated insensitivity to Erdafitinib (JNJ-42756493) in culture (PMID: 28341788). 28341788
KRAS G12V colon cancer sensitive Luminespib Preclinical - Cell culture Actionable In a preclinical study, Luminespib (AUY922) inhibited growth of colon cancer cell lines harboring KRAS G12V in culture (PMID: 26832792). 26832792
KRAS G12V non-small cell lung carcinoma sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of non-small cell lung cancer cells harboring KRAS G12V in culture (PMID: 23629727). 23629727
KRAS G12V pancreatic ductal adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12V demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
KRAS G12V colorectal cancer sensitive Oxaliplatin Preclinical Actionable In a preclinical study, sensitivity to Eloxatin (oxaliplatin) was increased in colorectal tumor cell lines carrying KRAS G12V (PMID: 23209813). 23209813
KRAS G12V head and neck squamous cell carcinoma sensitive Sirolimus + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Rapamune (sirolimus) worked synergistically with Mekinist (trametinib) to inhibit proliferation of head and neck squamous carcinoma cell lines overexpressing KRAS G12V in culture and to reduce tumor growth in cell line xenograft models (PMID: 26882569). 26882569
KRAS G12V ovarian serous carcinoma sensitive Selumetinib Clinical Study Actionable In a clinical case study, treatment with Selumetinib (AZD6244) resulted in lack of tumor progression for greater than 7 years in patient with low grade serous ovarian carcinoma harboring KRAS G12V (PMID: 27231576). 27231576
KRAS G12V colorectal cancer sensitive AZD4785 Preclinical - Cell culture Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of colorectal cancer cell lines harboring KRAS G12V (PMID: 28615361). 28615361
KRAS G12V lung cancer sensitive 7RH + LY411575 Preclinical Actionable In a preclinical study, 7RH and LY411575 combination treatment resulted in additive effect on apoptosis in KRAS G12V-driven animal models of lung cancer (PMID: 26855149). 26855149
KRAS G12V colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring KRAS G12V were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). 25838391
KRAS G12V 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 KRAS G12V in culture, while single agent inhibition had no effect (PMID: 26140595). 26140595
KRAS G12V lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12V mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12V colorectal cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) decreased viability of a colorectal cancer cell line harboring KRAS G12V in culture (PMID: 27602501). 27602501
KRAS G12V non-small cell lung carcinoma predicted - sensitive Selumetinib + Docetaxel Phase I Actionable In a Phase I study, NSCLC patients harboring KRAS G12C or G12V mutations demonstrated a trend towards better overall survival, progression free survival, and objective response rate compared to NSCLC patients with other KRAS mutations when treated with the combination therapy, Selumetinib (AZD6244) and Taxotere (docetaxel) (PMID: 26125448). 26125448
KRAS G12V 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 KRAS G12V in culture (PMID: 25838391). 25838391
KRAS G12V colorectal cancer decreased response Neratinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring KRAS G12V were less sensitive to Nerlynx (neratinib) induced growth inhibition in culture (PMID: 26243863). 26243863
KRAS G12V pancreatic ductal adenocarcinoma sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS G12V (PMID: 30045908). 30045908
KRAS G12V colon cancer sensitive AZ-TAK1 Preclinical - Cell culture Actionable In a preclinical study, a colon cancer cell line harboring KRAS G12V demonstrated sensitivity to AZ-TAK1 in culture, resulting in inhibition of cell growth (PMID: 27655129). 27655129
KRAS G12V colorectal cancer sensitive 3144 Preclinical - Cell culture Actionable In a preclinical study, 3144 inhibited growth of a colorectal cancer cell line harboring KRAS G12V in culture (PMID: 28235199). 28235199
KRAS G12V pancreatic ductal adenocarcinoma sensitive SHP099 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Mekinist (trametinib) and SHP099 led to reduced cell viability in pancreatic ductal adenocarcinoma cells harboring KRAS G12V in culture (PMID: 30045908). 30045908
KRAS G12V colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G12V mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12V lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12V mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12V lung cancer sensitive Aurora Kinase Inhibitor II Preclinical - Cell culture Actionable In a preclinical study, Aurora Kinase Inhibitor II (AI II) decreased viability of transformed lung cells expressing KRAS G12V in culture (PMID: 26842935). 26842935
KRAS G12V colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring KRAS G12V were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
PIK3CA R88Q PTEN mut KRAS G12V endometrial cancer decreased response BEZ235 Preclinical Actionable In a preclinical study, endometrial cancer cells harboring PIK3CA R88Q. PTEN mutations, and KRAS G12V demonstrated decreased sensitivity to BEZ235 compared with cells without KRAS mutations in culture (PMID: 22662154). 22662154
PIK3CA R88Q PTEN mut KRAS G12V endometrial cancer decreased response Everolimus Preclinical Actionable In a preclinical study, endometrial cancer cells harboring PIK3CA R88Q. PTEN mutations, and KRAS G12V demonstrated decreased sensitivity to Afinitor (everolimus) compared with cells without KRAS mutations in culture (PMID: 22662154). 22662154
KRAS G12V PIK3CA E545K TP53 R335fs colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12V, PIK3CA E545K, and TP53 R335fs (PMID: 26272063). 26272063
KRAS G12V MET amp carcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical case study, a patient with a carcinoma of unknown primary harboring MET amplification and KRAS G12V demonstrated a durable response following treatment with Xalkori (crizotinib) (PMID: 25232318). 25232318
KRAS G12V TP53 del lung cancer resistant 7RH Preclinical Actionable In a preclinical study, 7RH treatment had no effect on tumor cell apoptosis in KRAS G12V-driven animal models of lung cancer with TP53 knockout background (PMID: 26855149). 26855149
KRAS G12V TP53 del lung cancer sensitive 7RH + LY411575 Preclinical Actionable In a preclinical study, 7RH and LY411575 combination treatment induced apoptosis in KRAS G12V-driven animal models of lung cancer with TP53 knockout background (PMID: 26855149). 26855149
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer sensitive Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment resulted in enhanced tumor growth stabilization compared to single agent in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer decreased response BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
KRAS G12V PIK3CA E545K TP53 wild-type colorectal cancer decreased response Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12V and PIK3CA E545K (PMID: 26272063). 26272063
BRAF wild-type KRAS G12V non-small cell lung carcinoma resistant GDC0879 Preclinical - Pdx Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells harboring KRAS G12V in patient-derived xenograft models (PMID: 19276360). 19276360
KRAS G12V EZH2 pos lung adenocarcinoma no benefit DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12V (PMID: 26676756). 26676756
KRAS G12V EZH2 pos lung adenocarcinoma no benefit DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to Selumetinib (AZD6244) in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12V (PMID: 26676756). 26676756
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
EGFR L858R KRAS G12V lung adenocarcinoma resistant Afatinib + Cetuximab Preclinical Actionable In a preclinical study, KRAS G12V was detected in animal models of EGFR L858R-induced lung adenocarcinoma, which developed after repeated Gilotrif (afatinib) and Erbitux (cetuximab) combination treatments and resulted in drug resistance (PMID: 26341921). 26341921
KRAS exon 3 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with KRAS exon 3 mutations (NCCN.org). detail...
KRAS exon 3 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 3 mutations (NCCN.org). detail...
KRAS exon 3 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 3 mutations (NCCN.org). detail...
KRAS exon 3 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with KRAS exon 3 mutations (NCCN.org). detail...
KRAS exon 4 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with KRAS exon 4 mutations (NCCN.org). detail...
KRAS exon 4 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with KRAS exon 4 mutation (NCCN.org). detail...
KRAS exon 4 colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with KRAS exon 4 mutation (NCCN.org). detail...
KRAS exon 4 colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with KRAS exon 4 mutations (NCCN.org). detail...
KRAS A146T colorectal cancer resistant Cetuximab Preclinical - Cell line xenograft Actionable In a preclinical study, a colorectal cancer cell line harboring KRAS A146T demonstrated resistance to tumor growth inhibition by Erbitux (cetuximab) in xenograft models (PMID: 20570890). 20570890
KRAS A146T colorectal cancer sensitive PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring KRAS A146T in culture and in cell line xenograft models (PMID: 20570890). 20570890
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 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 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 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 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
KRAS G13C PIK3CA H1047Y PTEN G143fs PTEN K267fs ovarian clear cell adenocarcinoma sensitive DS-7423 Preclinical - Cell line xenograft Actionable In a preclinical study, an ovarian clear cell adenocarcinoma cell line harboring KRAS G13C, PIK3CA H1047Y, PTEN G143fs, and PTEN K267fs was sensitive to treatment with DS-7423, demonstrating inhibition of cell proliferation in culture and tumor growth inhibition in xenograft models (PMID: 24504419). 24504419
EGFR amp FGFR1 amp KRAS G13C lung cancer resistant Erdafitinib Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line with co-amplification of FGFR1 and EGFR and harboring KRAS G13C demonstrated insensitivity to Erdafitinib (JNJ-42756493) in culture (PMID: 28341788). 28341788
KRAS G13C lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G13C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G13C lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G13C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12C PTPN11 P491Q pancreatic ductal adenocarcinoma resistant Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12C and expressing PTPN11 P491Q were resistant to the combination therapy, Selumetinib (AZD6244) and SHP099, in culture (PMID: 30045908). 30045908
KRAS G12C PIK3CA H1047R TP53 R248W colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12C, PIK3CA H1047R, and TP53 R248W (PMID: 26272063). 26272063
EML4-ALK KRAS G12C non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and KRAS G12C demonstrated a minimal response when treated with Xalkori (crizotinib), and eventually progressed (PMID: 29636358). 29636358
KRAS G12C pancreatic ductal adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12C demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
KRAS G12C non-small cell lung carcinoma predicted - sensitive GLPG0634 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring KRAS G12C in culture that had, over time, acquired resistance to Selumetinib (AZD6244) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401). 28729401
KRAS G12C pancreatic adenocarcinoma sensitive Refametinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including Refametinib (BAY86-9766), in culture (PMID: 28957417). 28957417
KRAS G12C pancreatic adenocarcinoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including Mekinist (trametinib), in culture (PMID: 28957417). 28957417
KRAS G12C Advanced Solid Tumor sensitive ARS-853 Preclinical Actionable In a preclinical study, ARS-853 inhibited growth of several human tumor cell lines harboring KRAS G12C in 3-dimensional culture conditions (PMID: 26739882). 26739882
KRAS G12C non-small cell lung carcinoma sensitive SML-10-70-1 Preclinical - Cell culture Actionable In a preclinical study, SML-10-70-1 inhibited proliferation and Erk/Akt signaling in non-small cell lung cancer cells expressing KRAS G12C in culture (PMID: 24259466). 24259466
KRAS G12C non-small cell lung carcinoma sensitive CID1067700 Preclinical Actionable In a preclinical study, CID1067700 inhibited growth and increased apoptosis of non-small cell lung cancer cells that harbor KRAS G12C in culture (PMID: 26247207, PMID: 19477428). 26247207 19477428
KRAS G12C lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12C 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 KRAS G12C in culture (PMID: 25665005). 25665005
KRAS G12C 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 lung cells harboring KRAS G12C in culture (PMID: 25665005). 25665005
KRAS G12C lung cancer sensitive AZD4785 Preclinical - Pdx Actionable In a preclinical study, AZD4785 inhibited Kras expression and downstream signaling, resulted in tumor growth inhibition in patient-derived xenograft models of lung cancer harboring KRAS G12C (PMID: 28615361). 28615361
KRAS G12C non-small cell lung carcinoma predicted - sensitive Selumetinib + Docetaxel Phase I Actionable In a Phase I study, NSCLC patients harboring KRAS G12C or G12V mutations demonstrated a trend towards better overall survival, progression free survival, and objective response rate compared to NSCLC patients with other KRAS mutations when treated with the combination therapy, Selumetinib (AZD6244) and Taxotere (docetaxel) (PMID: 26125448). 26125448
KRAS G12C pancreatic cancer sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human pancreatic cancer cell line harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, treatment with Nexavar (sorafenib) resulted in partial response (PR) in 8.8% (5/57) and stable disease (SD) in 43.8% (25/57) of patients with KRAS-mutant non-small cell lung cancer, including SD in 12 patients and PR in 3 patients with KRAS G12C (PMID: 23224737). 23224737
KRAS G12C pancreatic ductal adenocarcinoma sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS G12C (PMID: 30045908). 30045908
KRAS G12C pancreatic cancer sensitive GDC-0623 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC-0623 induced tumor regression in pancreatic cancer cell line xenograft models harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C pancreatic ductal adenocarcinoma sensitive SHP099 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Mekinist (trametinib) and SHP099 led to reduced cell viability in pancreatic ductal adenocarcinoma cells harboring KRAS G12C in culture (PMID: 30045908). 30045908
KRAS G12C lung adenocarcinoma sensitive Afatinib Preclinical - Pdx Actionable In a preclinical study, a lung adenocarcinoma patient-derived xenograft (PDX) model was sensitive to treatment with Gilotrif (afatinib), demonstrating inhibition of tumor growth (PMID: 29925635). 29925635
KRAS G12C colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G12C mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12C lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12C mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12C pancreatic adenocarcinoma sensitive BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, BI-847325 induced sustained tumor regression in pancreatic adenocarcinoma cell line xenograft models harboring KRAS G12C (PMID: 27496137). 27496137
KRAS G12C pancreatic adenocarcinoma sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by Selumetinib (AZD6244) in culture (PMID: 28957417). 28957417
KRAS G12C lung cancer sensitive SCH772984 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and SCH772984 combination treatment demonstrated enhanced growth inhibition and sustained inhibition of Erk signaling in lung cancer cells harboring KRAS G12C in culture (PMID: 27338794). 27338794
KRAS G12C non-small cell lung carcinoma sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of a human non-small cell lung cancer cell line harboring KRAS G12C (PMID: 23934108). 23934108
KRAS G12C pancreatic adenocarcinoma sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a pancreatic adenocarcinoma cell line harboring KRAS G12C demonstrated sensitivity to growth inhibition by MEK inhibitors, including PD-0325901, in culture (PMID: 28957417). 28957417
KRAS G12C non-small cell lung carcinoma predicted - sensitive Docetaxel + Trametinib Phase I Actionable In a Phase I/Ib trial, the subgroup of non-small cell lung cancer patients harboring KRAS G12C demonstrated a disease control rate (DCR) of 80% (8/10; 4 partial responses, 4 stable disease) following treatment with the combination of Mekinist (trametinib) and Taxotere (docetaxel), compared to a DCR of 60% (15/25) in the overall KRAS-mutant population (PMID: 27876675). 27876675
KRAS G12C pancreatic cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human pancreatic cancer cell lines harboring KRAS G12C in culture (PMID: 21325073, PMID: 12068308). 21325073 12068308
KRAS G12C colorectal cancer sensitive Cetuximab + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Mekinist (trametinib) decreased viability of colorectal cancer cells harboring KRAS G12C in culture (PMID: 28179366). 28179366
KRAS G12C non-small cell lung carcinoma sensitive AZD4785 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of non-small cell lung carcinoma cell lines harboring KRAS G12C, and anti-tumor activity in cell line xenograft models (PMID: 28615361). 28615361
KRAS G12C non-small cell lung carcinoma sensitive ARS-853 Preclinical - Cell culture Actionable In a preclinical study, ARS-853 treatment in culture resulted in decreased cell proliferation and apoptotic induction in non-small cell lung carcinoma cells harboring KRAS G12C (PMID: 26841430). 26841430
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
KRAS G12C EZH2 pos lung adenocarcinoma sensitive Selumetinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, the addition of Tazemetostat (EPZ-6438) increased sensitivity to Selumetinib (AZD6244) in EZH2-expressing lung adenocarcinoma cell lines harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos pancreatic cancer sensitive DZNep + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to Selumetinib (AZD6244) in an EZH2-expressing pancreatic cancer cell line harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos lung adenocarcinoma sensitive GSK343 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of GSK343 increased sensitivity to Selumetinib (AZD6244) in EZH2-expressing lung adenocarcinoma cell lines harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos lung adenocarcinoma no benefit MK2206 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, the addition of Tazemetostat (EPZ-6438) did not increase sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos pancreatic cancer sensitive DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep increased sensitivity to MK2206 in an EZH2-expressing pancreatic cancer cell line harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos lung adenocarcinoma no benefit DZNep + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of DZNep did not increase sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12C (PMID: 26676756). 26676756
KRAS G12C EZH2 pos lung adenocarcinoma no benefit GSK343 + MK2206 Preclinical - Cell culture Actionable In a preclinical study, the addition of GSK343 did not increase sensitivity to MK2206 in an EZH2-expressing lung adenocarcinoma cell line harboring KRAS G12C in culture (PMID: 26676756). 26676756
KRAS G12C EZH2 pos lung adenocarcinoma sensitive DZNep + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of DZNep increased sensitivity to Selumetinib (AZD6244) in EZH2-expressing lung adenocarcinoma cell lines harboring KRAS G12C, in culture and in xenograft models, resulting in decreased cell survival and tumor growth (PMID: 26676756). 26676756
BRAF wild-type KRAS G12C non-small cell lung carcinoma resistant GDC0879 Preclinical - Pdx Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells harboring KRAS G12C in patient-derived xenograft models (PMID: 19276360). 19276360
KRAS G12F PIK3CA H1047R lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12F and PIK3CA H1047R (PMID: 26855149). 26855149
PIK3CA mutant KRAS Q61X ovarian carcinoma sensitive Bevacizumab + Temsirolimus + Doxil Clinical Study Actionable In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in a patient with ovarian carcinoma harboring both a PIK3CA mutation and a KRAS Q61 mutation (PMID: 21216929). 21216929
KRAS Q61L PIK3CA E542K TP53 T118Qfs*5 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, but did not induce apoptosis in colorectal cancer cells harboring KRAS Q61L, PIK3CA E542K, and TP53 T118Qfs*5 in culture (PMID: 26272063). 26272063
KRAS G13X lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a clinical study, KRAS codon 12 or 13 mutations correlated with a lack of response to Iressa (gefitinib) in patients with lung adenocarcinoma (PMID: 15696205). 15696205
KRAS G13X colorectal cancer sensitive Oxaliplatin Preclinical Actionable In a preclinical study, sensitivity to Eloxatin (oxaliplatin) was increased in colorectal tumor cell lines carrying KRAS codon 12 or 13 mutations (PMID: 23209813). 23209813
KRAS G13X colorectal cancer no benefit Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer (PMID: 26341920). 26341920
KRAS G13X colorectal cancer resistant Panitumumab Phase III Actionable In a Phase III trial, Vectibix (panitumumab) did not demonstrate efficacy in patients with metastatic colorectal cancer harboring KRAS mutations in codons 12 or 13 (PMID: 18316791; NCT00113763). 18316791
KRAS G12R thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited Erk activation and growth of thyroid cancer cells harboring KRAS G12R in culture, and reduced tumor size in cell line xenograft models (PMID: 26324075). 26324075
KRAS G12R pancreatic ductal adenocarcinoma predicted - sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Selumetinib (AZD6244) and SHP099 resulted in a synergistic effect, demonstrating reduced cell proliferation and decreased colony formation in pancreatic ductal adenocarcinoma cells harboring KRAS G12R (PMID: 30045908). 30045908
KRAS G12R thyroid cancer sensitive Pazopanib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination of Mekinist (trametinib) and Votrient (pazopanib) significantly delayed tumor progression in cell line xenograft models of thyroid cancer harboring KRAS G12R (PMID: 26324075). 26324075
KRAS G12R thyroid cancer sensitive Pazopanib Preclinical - Cell line xenograft Actionable In a preclinical study, Votrient (pazopanib) inhibited Erk activation and growth of thyroid cancer cells harboring KRAS G12R in culture, and reduced tumor size in cell line xenograft models (PMID: 26324075). 26324075
KRAS G12R lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12R mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS G12R colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring a KRAS G12R mutation demonstrated resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G12R pancreatic ductal adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, pancreatic ductal adenocarcinoma cells harboring KRAS G12R demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture when compared to the combined therapy of Selumetinib (AZD6244) and SHP099 (PMID: 30045908). 30045908
KRAS G12R lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS G12R mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer resistant Dasatinib Preclinical - Cell line xenograft Actionable In a preclinical study, thyroid cancer cell lines harboring HRAS G13R and KRAS G12R with an acquired SRC T341M mutation demonstrated resistance to Sprycel (dasatinib) in culture and in cell line xenograft models (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M 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 thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of Sprycel (dasatinib)-resistant thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M in culture and in cell line xenograft models (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Dasatinib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture, and resulted in sustained tumor suppression and prolonged survival in cell line xenograft models (PMID: 27222538). 27222538
HRAS G13R KRAS G12R SRC T341M thyroid cancer sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of Sprycel (dasatinib)-resistant thyroid cancer cell lines harboring KRAS G13R, HRAS G12R, and an acquired SRC T341M mutation in culture (PMID: 27222538). 27222538
EGFR L858R KRAS G12R lung adenocarcinoma resistant Afatinib + Cetuximab Preclinical Actionable In a preclinical study, KRAS G12R was detected in animal models of EGFR L858R-induced lung adenocarcinoma, which developed after repeated Gilotrif (afatinib) and Erbitux (cetuximab) combination treatments and resulted in drug resistance (PMID: 26341921). 26341921
KRAS G12R TP53 R248L lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12R and TP53 R248L (PMID: 26855149). 26855149
KRAS G13D PIK3CA D549N PIK3CA E545K 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 KRAS G13D, PIK3CA D549N, and PIK3CA E545K in culture (PMID: 23629727). 23629727
KRAS G13D PIK3CA D549N PIK3CA E545K colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited Mapk and Akt signaling, resulted in growth inhibition of colorectal cancer cells harboring KRAS G13D, PIK3CA D549N, and PIK3CA E545K in culture and in cell line xenograft models (PMID: 23629727). 23629727
KRAS G13D PIK3CA D549N PIK3CA E545K colorectal cancer decreased response Pimasertib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring KRAS G13D, PIK3CA D549N and PIK3CA E545K demonstrated decreased response to Pimasertib (MSC1936369B) in culture (PMID: 23629727). 23629727
KRAS G13D PIK3CA D549N PIK3CA E545K 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 KRAS G13D, PIK3CA D549N, and PIK3CA E545K in culture (PMID: 23629727). 23629727
KRAS G13D PIK3CA D549N PIK3CA E545K colorectal cancer sensitive Pimasertib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Pimasertib (MSC1936369B) and BEZ235 combination treatment inhibited tumor growth in colorectal cancer cell line xenograft models harboring KRAS G13D, PIK3CA D549N, and PIK3CA E545K (PMID: 23629727). 23629727
KRAS G13D colorectal cancer sensitive LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited growth of, and blocked MAPK signaling in human colorectal cancer cells harboring KRAS G13D in culture (PMID: 26343583). 26343583
KRAS G13D 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 KRAS G13D in culture (PMID: 23629727). 23629727
KRAS G13D colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) synergistically inhibited growth of colorectal cancer cells harboring KRAS G13D in culture and resulted in partial tumor regression in patient-derived xenograft models (PMID: 26369631). 26369631
KRAS G13D colorectal cancer sensitive rigosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Estybon (rigosertib) inhibited Mek/Erk signaling and tumor growth in cell line xenograft models of colorectal cancer harboring KRAS G13D (PMID: 27104980). 27104980
KRAS G13D 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 KRAS G13D in culture (PMID: 23629727). 23629727
KRAS G13D colorectal adenocarcinoma sensitive RO5126766 Preclinical - Cell culture Actionable In a preclinical study, RO5126766 inhibited proliferation of colorectal adenocarcinoma cells harboring KRAS G13D in culture (PMID: 26438159). 26438159
KRAS G13D colon cancer sensitive Luminespib Preclinical - Cell line xenograft Actionable In a preclinical study, a colon cancer cell line harboring KRAS G13D demonstrated increased sensitivity to Luminespib (AUY922) compared to cell lines with wild-type KRAS, resulting in decreased viability and increased apoptosis in culture and reduced tumor growth in xenograft models (PMID: 26832792). 26832792
KRAS G13D colon cancer no benefit Buparlisib Preclinical Actionable In a preclinical studu, BKM120 alone failed to induce tumor regression in mouse xenograft models of Kras G13D mutant colorectal cancer (PMID: 24576621). 24576621
KRAS G13D colorectal adenocarcinoma sensitive RO4987655 Preclinical - Cell culture Actionable In a preclinical study, RO4987655 inhibited proliferation of colorectal adenocarcinoma cells harboring KRAS G13D in culture (PMID: 26438159). 26438159
KRAS G13D colorectal cancer sensitive Oxaliplatin Preclinical Actionable In a preclinical study, sensitivity to Eloxatin (oxaliplatin) was increased in colon tumor cell lines carrying KRAS G13D (PMID: 23209813). 23209813
KRAS G13D 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 KRAS G13D in culture (PMID: 23629727). 23629727
KRAS G13D colorectal cancer resistant Sunitinib Preclinical Actionable In a preclinical study, a colorectal cancer cell line harboring the KRAS G13D mutation showed resistance to Sutent (sunitinib) treatment (PMID: 23455880). 23455880
KRAS G13D 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 in human colorectal cancer cell lines harboring KRAS G13D in culture (PMID: 25838391). 25838391
KRAS G13D colorectal cancer decreased response Neratinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring KRAS G13D were less sensitive to Nerlynx (neratinib) induced growth inhibition in culture (PMID: 26243863). 26243863
KRAS G13D colon cancer sensitive APS-2-79 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and Mekinist (trametinib) worked synergistically to decrease viability of a colon cancer cell line harboring KRAS G13D in culture (PMID: 27556948). 27556948
KRAS G13D colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring KRAS G13D were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
KRAS G13D colorectal adenocarcinoma predicted - sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD-6244) inhibited proliferation of colorectal adenocarcinoma cells harboring KRAS G13D in culture (PMID: 26438159). 26438159
KRAS G13D colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, KRAS mutations in codon 12 or 13 were associated with resistance to Erbitux (cetuximab) in colorectal cancer patients (PMID: 18202412). 18202412
KRAS G13D breast cancer sensitive 3144 Preclinical - Cell line xenograft Actionable In a preclinical study, 3144 inhibited growth of a breast cancer cell line harboring KRAS G13D in culture and reduced tumor growth in xenograft models (PMID: 28235199). 28235199
KRAS G13D non-small cell lung carcinoma sensitive AZD4785 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of non-small cell lung carcinoma cells harboring KRAS G13D, and anti-tumor activity in cell line xenograft models (PMID: 28615361). 28615361
KRAS G13D Advanced Solid Tumor sensitive GDC-0623 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC-0623 demonstrated efficacy against both KRAS-mutant and BRAF-mutant cancer models in cell based assays and cell line xenografts (PMID: 23934108). 23934108
KRAS G13D colorectal cancer sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) inhibited tumor growth in xenograft models of human colorectal cancer cell lines harboring KRAS G13D (PMID: 23934108). 23934108
KRAS G13D colorectal cancer sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of colorectal cancer cells harboring KRAS G13D in culture (PMID: 29343524). 29343524
KRAS G13D colorectal cancer decreased response Pimasertib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring KRAS G13D demonstrated decreased response to Pimasertib (MSC1936369B) in culture (PMID: 23629727). 23629727
BRAF wild-type KRAS G13D colon cancer resistant GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type colon cancer cells harboring KRAS G13D in culture ann in cell line xenograft models (PMID: 19276360). 19276360
KRAS G13D PIK3CA H1047R colon cancer sensitive PD-0325901 + Gedatolisib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gedatolisib (PF-05212384) and PD-0325901 inhibited tumor growth in colon cancer cell line xenograft models harboring KRAS G13D and PIK3CA H1047R (PMID: 21325073). 21325073
KRAS G13D PIK3CA H1047R colon cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human colon cancer cells harboring KRAS G13D and PIK3CA H1047R in culture (PMID: 21325073, PMID: 24042735). 21325073 24042735
KRAS G13D PIK3CA H1047R colon cancer sensitive Gedatolisib + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, Gedatolisib (PKI-587) and Camptostar (irinotecan) synergistically suppressed the growth of a human colon cancer cell line harboring KRAS G13D and PIK3CA H1047R (PMID: 24042735) in xenograft models (PMID: 21325073). 21325073 24042735
KRAS G13D PIK3CA H1047R colon cancer sensitive CC-223 Preclinical Actionable In a preclinical study, CC-223 inhibited proliferation of HCT-116 colon cancer cells, which have been reported to harbor KRAS G13D and PIK3CA H1047R mutations, in culture (PMID: 25855786, PMID: 24978597). 25855786 24978597
KRAS G13D PIK3CA H1047R colon cancer sensitive Irinotecan Preclinical Actionable In a preclinical study, Camptostar (irinotecan) suppressed the growth of a human colon cancer cell line harboring KRAS G13D and PIK3CA H1047R in xenograft models (PMID: 21325073, PMID: 16707468). 21325073 16707468
KRAS G13D PIK3CA H1047R colorectal cancer sensitive Regorafenib + Cetuximab Preclinical - Cell line xenograft 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 KRAS G13D and PIK3CA H1047R in culture, and reduced tumor growth in cell line xenograft models (PMID: 25838391). 25838391
KRAS G13D PIK3CA H1047R colon cancer sensitive Gedatolisib + Camptothecin Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) and Camptothecin in combination synergistictically enhanced Parp cleavage in a human colon cancer cell line harboring KRAS G13D and PIK3CA H1047R in culture (PMID: 21325073, PMID: 24042735). 25688157 24042735
KRAS G13D PIK3CA H1047R colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cells harboring KRAS G13D and PIK3CA H1047R were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
KRAS G13D PIK3CA H1047R colon cancer sensitive AT-7867 Preclinical Actionable In a preclinical study, AT-7867 inhibited proliferation of cultured HCT-116 colon cancer cells, which have been reported to harbor KRAS G13D and PIK3CA H1047R mutations (PMID: 20423992, PMID: 24978597). 24978597 20423992
KRAS G13D PIK3CA H1047R colorectal cancer sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Alpelisib (BYL719) decreased viability of a colorectal cancer cell line harboring KRAS G13D and PIK3CA H1047R in culture (PMID: 27602501). 27602501
KRAS G13D PIK3CA H1047R colon cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited tumor growth in xenograft models of a human colon cancer cell line harboring KRAS G13D and PIK3CA H1047R mutations (PMID: 21558396). 21558396
KRAS G13D PIK3CA H1047R colon cancer sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 induced caspase activation in a human colon cancer cell line harboring KRAS G13D and PIK3CA H1047R in culture (PMID: 20570890, PMID: 22693356). 20570890 22693356
KRAS G13D PIK3CA E545k TP53 S241F 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, but did not induce apoptosis in colorectal cancer cells harboring KRAS G13D, PIK3CA E545K, and TP53 S241F in culture (PMID: 26272063). 26272063
ERBB2 over exp KRAS G13D 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 G13D in 1 patient demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
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 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 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 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 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 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 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 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 + 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
KRAS G13D PIK3CA E545K colorectal adenocarcinoma sensitive Cobimetinib + Pictilisib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Pictilisib (GDC-0941) and Cobimetinib (GDC-0973) inhibited tumor growth in a colorectal adenocarcinoma xenograft model harboring KRAS G13D and PIK3CA E545K mutations, and demonstrated improved efficacy over either agent alone (PMID: 22084396). 22084396
KRAS G13D PIK3CA E545K endometrial cancer resistant Everolimus Preclinical - Cell line xenograft Actionable In a preclinical study, expression of KRAS G13D in an endometrial cancer cell line harboring PIK3CA E545K conferred resistance to Afinitor (everolimus) in xenograft models (PMID: 20664172). 20664172
KRAS G13D PIK3CA H1047R 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 KRAS G13D and PIK3CA H1047R in culture and in cell line xenograft models (PMID: 26272063). 26272063
BRAF G464V KRAS G13D breast cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring BRAF G464V and KRAS G13D in culture (PMID: 21325073, PMID: 17314276). 17314276 21325073
BRAF G464V KRAS G13D breast cancer sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of breast cancer cells harboring BRAF G464V and KRAS G13D in culture and inhibited angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). 21170960
BRAF G464V KRAS G13D breast cancer decreased response CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 demonstrated decreased response to tumor growth inhibition in xenograft models of human breast cancer cell lines harboring KRAS G13D and BRAF G464V (PMID: 21558396). 21558396
BRAF G464V KRAS G13D triple-receptor negative breast cancer sensitive DHM25 Preclinical - Cell line xenograft Actionable In a preclinical study, DHM25 increased cell death and decreased migration of a triple-negative breast cancer cell line harboring KRAS G13D and BRAF G464V in culture, and reduced tumor growth and lung metastasis in xenograft models (PMID: 26237138). 26237138
KRAS G13D PIK3CA E545K PIK3CA D549N colon cancer decreased response Gedatolisib Preclinical Actionable In a preclinical study, human colon cancer cells harboring KRAS G13D, PIK3CA E545K, and PIK3CA D549N had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073, PMID: 24042735). 21325073 24042735
KRAS G13D PIK3CA E545K PIK3CA D549N colorectal cancer resistant Regorafenib Preclinical Actionable In a preclinical study, human colorectal cancer cell lines harboring KRAS G13D, PIK3CA E545K and PIK3CA D549N were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). 25838391
KRAS G13D PIK3CA E545K PIK3CA D549N colorectal cancer sensitive Regorafenib + Cetuximab Preclinical - Cell line xenograft 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 KRAS G13D, PIK3CA E545K, and PIK3CA D549N in culture and reduced tumor growth in cell line xenograft models (PMID: 25838391). 25838391
EML4-ALK KRAS G13D non-small cell lung carcinoma predicted - resistant Crizotinib Clinical Study Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK eventually progressed while on treatment with Xalkori (crizotinib) and was subsequently found to harbor a presumed resistance mutation, KRAS G13D (PMID: 29636358). 29636358
MAP2K1 Y134C KRAS Q61H lung adenocarcinoma no benefit Refametinib Preclinical Actionable In a preclinical study, treatment with Refametanib (BAY86-9766) had no effect on a lung adenocarcinoma cell line co-harboring MAP2K1 Y134C and KRAS Q61H in culture (PMID: 26582713). 26582713
MAP2K1 Y134C KRAS Q61H lung adenocarcinoma no benefit Trametinib Preclinical Actionable In a preclinical study, treatment with Mekinist (trametinib) had no effect on a lung adenocarcinoma cell line co-harboring MAP2K1 Y134C and KRAS Q61H in culture (PMID: 26582713). 26582713
KRAS Q61H ovarian carcinoma sensitive Bevacizumab + Sorafenib Clinical Study Actionable In a clinical case study, a patient with ovarian carcinoma harboring KRAS Q61H demonstrated sensitivity to treatment with the combination of Nexavar (sorafenib) and Avastin (bevacizumab), resulting in 62% tumor regression (PMID: 25363205). 25363205
KRAS Q61H non-small cell lung carcinoma sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 inhibited growth and repressed RAF-MEK-MAPK signaling as indicated by reduced phosphorylation of Craf, Mek, and Mapk in a human non-small cell lung cancer cell line harboring KRAS Q61H in culture (PMID: 19165201, PMID: 22693356). 22693356 19165201
KRAS Q61H lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS Q61H mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS Q61H lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS Q61H mutation due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS Q61H non-small cell lung carcinoma resistant Pictilisib Preclinical Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring KRAS Q61H (PMID: 19165201) were insensitive to pictilisib (GDC-0941) growth inhibition in culture (PMID: 22693356). 22693356 19165201
KRAS Q61H non-small cell lung carcinoma sensitive AZD4785 Preclinical - Cell culture Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of non-small cell lung carcinoma cell lines harboring KRAS Q61H (PMID: 28615361). 28615361
KRAS Q61H PIK3CA E542K colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment resulted in partial tumor regression in PDX models of colorectal cancer cells harboring KRAS Q61H and PIK3CA E542K (PMID: 26369631). 26369631
KRAS Q61H PIK3CA E545K non-small cell lung carcinoma sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS Q61H and PIK3CA E545K in culture (PMID: 23629727). 23629727
KRAS Q61H PIK3CA E545K non-small cell lung carcinoma decreased response Pimasertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring KRAS Q61H and PIK3CA E545K demonstrated decreased response to Pimasertib (MSC1936369B) in culture (PMID: 23629727). 23629727
KRAS Q61H PIK3CA E545K non-small cell lung carcinoma sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS Q61H and PIK3CA E545K in culture (PMID: 23629727). 23629727
KRAS Q61H PIK3CA E545K non-small cell lung carcinoma sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring KRAS Q61H and PIK3CA E545K in culture (PMID: 23629727). 23629727
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
KRAS mut STK11 mut non-small cell lung carcinoma predicted - resistant unspecified PD-1 antibody Phase III Actionable In a Phase III trial, non-small cell lung carcinoma patients co-harboring a KRAS mutation and STK11 mutation demonstrated an objective response rate (ORR) of 0% (0/6) when treated with Opdivo (nivolumab) compared to an ORR of 57.1% (4/7) in patients co-harboring a KRAS mutation and TP53 mutation and an ORR of 18.2% (2/11) in patients with mutant KRAS only (PMID: 29773717; NCT01673867). 29773717
KRAS mut STK11 mut non-small cell lung carcinoma sensitive PKI-402 Preclinical - Cell line xenograft Actionable In a preclinical study, PKI-402 inhibited growth of a non-small cell lung cancer cell line harboring both KRAS and STK11 mutations in culture and in cell line xenograft models (PMID: 20371716). 20371716
KRAS mut STK11 mut lung adenocarcinoma predicted - resistant unspecified PD-1 antibody Clinical Study Actionable In a clinical study, lung adenocarcinoma patients co-harboring a KRAS mutation and STK11 mutation demonstrated a lower objective response rate (7.4% vs 35.7% vs 28.6%) and shorter PFS (1.8mo vs 3.0 vs 2.7) and OS (6.4mo vs 16 vs 16.1) compared to patients with KRAS and TP53 mutations and patients with KRAS mutations only when treated with a PD-1 inhibitor (Nivolumab, n=146; Pembrolizumab, n=19) (PMID: 29773717). 29773717
KRAS mut + TP53 wild-type colorectal cancer sensitive ABT-263 + Alpelisib + CGM097 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Mekinist (trametinib), and CGM097 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a KRAS mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
KRAS mut + TP53 wild-type Advanced Solid Tumor sensitive Oxaliplatin + ABT-737 Preclinical Actionable In a preclinical study, Eloxatin (oxaliplatin), in combination with ABT-737, was only effective in tumor cell lines carrying KRAS mutants and wild-type TP53 (PMID: 21468686). 21468686
KRAS mut + TP53 wild-type colorectal cancer sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 induced activation of Tp53 target genes and inhibited growth of a colorectal cancer (CRC) cell line with wild-type TP53, that also harbored a KRAS mutation, in culture and inhibited tumor growth in a TP53 wild-type KRAS-mutant CRC cell line xenograft model (PMID: 25567130). 25567130
KRAS mut + TP53 wild-type colorectal cancer sensitive AMG 232 + Irinotecan Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of AMG 232 and Camptosaur (irinotecan) inhibited tumor growth in a TP53 wild-type colorectal cancer cell line xenograft model, which also harbors a KRAS mutation, with increased efficacy over either agent alone (PMID: 25567130). 25567130
APC mutant KRAS mutant KDR R961W colorectal cancer sensitive Regorafenib Clinical Study Actionable In a clinical case study, Stivarga (regorafenib) treatment resulted in durable partial response in a colorectal cancer patient harboring KDR R961W and mutations in APC and KRAS (PMID: 27004155). 27004155
FGFR2 dec exp KRAS mut lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr2 through shRNA did not sensitize KRAS mutant lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
KRAS mut TP53 G105C TP53 V157fs ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 G105C, V157fs and mutations in Kras (PMID: 27998224). 27998224
EGFR dec exp KRAS mut non-small cell lung carcinoma sensitive ER2 + Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of ER2 and Platinol (cisplatin) demonstrated synergy in inhibiting tumor growth in a non-small cell lung cancer cell line xenograft model with low expression of wild-type EGFR, that also harbors a KRAS mutation (PMID: 27040853). 27040853
EGFR dec exp KRAS mut lung adenocarcinoma sensitive GA201 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with GA201 induced antibody-dependent cell-mediated cytotoxicity against KRAS-mutant lung adenocarcinoma with low EGFR expression in culture and improved overall survival in low EGFR expressing, KRAS-mutant lung adenocarcinoma cell line xenograft models, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
EGFR dec exp KRAS mut non-small cell lung carcinoma sensitive GA201 Preclinical Actionable In a preclinical study, treatment with GA201 resulted in improved overall survival in KRAS-mutant non-small cell lung cancer cell line xenograft models with low EGFR expression, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
EGFR dec exp KRAS mut colorectal cancer sensitive GA201 Preclinical Actionable In a preclinical study, treatment with GA201 resulted in improved overall survival in KRAS-mutant colorectal cancer cell line xenograft models with low EGFR expression, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
FGFR3 dec exp KRAS mut lung cancer no benefit Trametinib Preclinical Actionable In a preclinical study, knocking down of Fgfr3 through shRNA did not sensitize KRAS mutant lung cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
KRAS mut PIK3CA mut non-small cell lung carcinoma sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 inhibited the growth of an Iressa (gefitinib)-resistant NSCLC cell line with KRAS and PIK3CA mutations (PMID: 24939055). 24939055
KRAS mut PIK3CA mut colorectal cancer resistant BEZ235 Preclinical Actionable In a preclinical study, colon cancer cells harboring KRAS and PIK3CA mutations demonstrated resistance to BEZ235 in culture and xenograft models (PMID: 23475782). 23475782
KRAS mut PIK3CA mut Advanced Solid Tumor sensitive CH5132799 Preclinical Actionable In a preclinical study, human solid tumor cell lines harboring coincident PIK3CA and KRAS mutations demonstrated sensitivity to CH5132799 in culture (PMID: 21558396). 21558396
KRAS mut PIK3CA mut non-small cell lung carcinoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) mildly inhibited the growth of an Iressa (gefitinib)-resistant NSCLC cell line with KRAS and PIK3CA mutations (PMID: 24939055). 24939055
KRAS mut PIK3CA mut stomach cancer predicted - sensitive Deguelin Preclinical Actionable In a preclinical study, Deguelin inhibited growth of the AGS gastric cancer cell line, which has been reported to harbor PIK3CA and KRAS mutations, in culture (PMID: 20811676, PMID: 24978597). 20811676 24978597
KRAS mut PIK3CA mut Advanced Solid Tumor sensitive Alpelisib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) inhibited growth in multiple tumor cell lines expressing PIK3CA mutations, and concurrent KRAS mutations was not associated with resistance (PMID: 24608574). 24608574
KRAS mut PIK3CA mut colorectal cancer no benefit Taselisib Phase I Actionable In a Phase I trial, a colorectal cancer patient co-harboring a PIK3CA mutation and KRAS mutation progressed on treatment with Taselisib (GDC-0032) (PMID: 28331003). 28331003
KRAS mut PIK3CA mut non-small cell lung carcinoma sensitive PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, PF-04691502 inhibited tumor growth in non-small cell lung cancer cell line xenograft models harboring both PIK3CA and KRAS mutations (PMID: 21750219). 21750219
KRAS mut PIK3CA mut Advanced Solid Tumor decreased response Taselisib Phase I Actionable In a Phase I trial, Taselisib (GDC-0032) demonstrated activity in patients with PIK3CA-mutant advanced solid tumors, but preliminary data analysis suggested the presence of a KRAS mutation was associated with lack of response (Cancer Res October 1, 2014 74:915). detail...
KRAS mut PIK3CA mut non-small cell lung carcinoma sensitive Buparlisib Phase II Actionable In a Phase II trial, one patient with Kras and Pikc3a mutant non-squamous NSCLC had a partial response to Buparlisib (BKM120) however, stage 2 of the study was not initiated due to failure of meeting overall stage 1 response endpoints (PMID: 26098748). 26098748
KRAS mut PIK3CA mut colon cancer sensitive GDC-0980 Preclinical - Cell line xenograft Actionable In a preclincal study, GDC-0980 delayed tumor growth in colon cancer cell line xenograft models harboring KRAS and PIKC3A mutations (PMID: 21998291). 21998291
KRAS mut PIK3CA mut non-small cell lung carcinoma sensitive Selumetinib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) in combination with BEZ235, synergistically prevented proliferation of an Iressa (gefitinib)-resistant NSCLC cell line harboring KRAS and PIK3CA mutations in culture and in cell line xenograft models (PMID: 24939055). 24939055
KRAS mut PIK3CA mut colon cancer sensitive A-443654 Preclinical Actionable In a preclinical study, A-443654 inhibited proliferation of colon cancer cell lines that have been reported to harbor KRAS and PIK3CA mutations in culture (PMID: 24569089, PMID: 24978597). 24978597 24569089
KRAS mut PIK3CA mut stomach cancer sensitive Buparlisib Preclinical Actionable In a preclinical study, BKM120 suppressed growth of a gastric cancer cell line harboring PIK3CA and KRAS mutations in culture (PMID: 22159814). 22159814
KRAS mut PIK3CA mut colon cancer sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 inhibited growth and induced apoptosis in a human colon cancer cell line harboring PIK3CA and KRAS mutations (PMID: 22693356). 22693356
KRAS mut PIK3CA mut colon cancer sensitive Copanlisib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Aliqopa (copanlisib) inhibited tumor growth in xenograft models of a human colon cancer cell line harboring PIK3CA and KRAS mutations (PMID: 24170767). 24170767
KRAS mut PIK3CA mut Advanced Solid Tumor resistant Everolimus Preclinical Actionable In a preclinical study, human cancer cells with PIK3CA mutations demonstrated sensitivity to Afinitor (everolimus), but a coincident KRAS mutation led to Afinitor (everolimus) resistance (PMID: 20664172). 20664174 20664172
KRAS mut PIK3CA mut colorectal cancer sensitive AZD8055 + Selumetinib Preclinical Actionable In a preclinical study, the combination of AZD8055 and Selumetinib (AZD6244) inhibited tumor growth in a colorectal cancer xenograft model harboring PIK3CA and KRAS mutations and had increased efficacy compared to either agent alone (PMID: 22271687). 22271687
KRAS mut PIK3CA mut colon cancer sensitive AT13148 Preclinical Actionable In a preclinical study, a colon cancer cell line harboring PIK3CA and KRAS mutations demonstrated sensitivity to AT13148 in culture (PMID: 22781553). 22781553
KRAS mut PIK3CA mut colorectal cancer sensitive CGM097 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CGM097 and Mekinist (trametinib) treatment compared to treatment with either agent alone in a colorectal cancer cell line resulted in a greater decrease in colony formation in culture, and improved stable disease in xenograft models (PMID: 27659046). 27659046
KRAS mut PIK3CA mut colorectal cancer sensitive SAR245409 Preclinical - Cell culture Actionable In a preclinical study, a colorectal cancer cell line co-harboring a KRAS mutation and PIK3CA mutation was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture (PMID: 24634413). 24634413
KRAS mut PIK3CA mut colorectal cancer sensitive ABT-263 + CGM097 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Navitoclax (ABT-263) improved the therapeutic effects of the combination of CGM097 and Mekinist (trametinib) in colorectal cancer cells, resulting in greater apoptotic activity and growth inhibition in culture, and tumor regression in xenograft models (PMID: 27659046). 27659046
KRAS mut + GATA2 wild-type non-small cell lung carcinoma sensitive bortezomib + fasudil Preclinical Actionable In a preclinical study, the combination of bortezomib and fasudil blocked GATA2 downstream signals in KRAS activated NSCLC cells, resulting in reduced tumor burden, size and number in treated mice (PMID: 22541434). 22541434
KRAS mutant PIK3CA H1047R colon cancer sensitive Buparlisib Preclinical Actionable In a preclinical study, Buparlisib (BKM120) inhibited proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA H1047R in culture (PMID: 26715098). 26715098
KRAS mutant PIK3CA H1047R colon cancer no benefit Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) did not inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA H1047R in culture (PMID: 26715098). 26715098
KRAS mutant PIK3CA H1047R colon cancer sensitive BKM120 + Cetuximab Preclinical Actionable In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA H1047R in culture (PMID: 26715098). 26715098
KRAS mut STK11 loss TP53 loss non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring KRAS mutation, STK11 and TP53 loss demonstrated increased sensitivity to MK-1775 and Platinol (cisplatin) combination treatment in culture compared to isogenic cell lines expressing wild-type Tp53 or Stk11 (PMID: 28652249). 28652249
KRAS mutant PIK3CA wild-type colorectal cancer predicted - sensitive TAK-733 Preclinical - Pdx & cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring mutations in KRAS or NRAS with wild-type PIK3CA demonstrated a trend toward increased sensitivity to TAK-733 in culture, and colorectal cancer patient-derived xenograft (PDX) models with KRAS or BRAF mutations and wild-type PIK3CA demonstrated a trend toward greater tumor growth inhibition (PMID: 26439693). 26439693
KRAS mutant PIK3CA wild-type colon cancer sensitive Buparlisib Preclinical Actionable In a preclinical study, Buparlisib (BKM120) inhibited proliferation of colon cancer cell lines harboring mutant KRAS and wild-type PIK3CA in culture and reduced tumor growth in xenograft models (PMID: 26715098). 26715098
KRAS mutant PIK3CA wild-type colon cancer sensitive BKM120 + Cetuximab Preclinical Actionable In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and wild-type PIK3CA in culture and tumor growth in xenograft models (PMID: 26715098). 26715098
EGFR pos KRAS mut triple-receptor negative breast cancer sensitive GA201 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with GA201 resulted in increased tumor growth inhibition in EGFR-positive triple-negative breast cancer cell line xenograft models harboring KRAS mutations when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
EGFR pos KRAS mut renal cell carcinoma sensitive GA201 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with GA201 resulted in improved overall survival in EGFR-positive renal cell carcinoma cell line xenograft models harboring KRAS mutations, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
EGFR pos KRAS mut pancreatic cancer sensitive GA201 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with GA201 resulted in improved overall survival in EGFR-positive pancreatic cancer cell line xenograft models harboring KRAS mutations, when compared to Erbitux (cetuximab) or vehicle control (PMID: 23209031). 23209031
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
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive Adavosertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations demonstrated increased sensitivity to MK-1775 compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive MK-1775 + Radiotherapy Preclinical - Cell culture Actionable In a preclinical study, MK-1775 combined with radiation therapy demonstrated enhanced growth inhibition in non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive MK-1775 + Cisplatin Preclinical - Cell culture Actionable In a preclinical study, MK-1775 and Platinol (cisplatin) combination treatment demonstrated enhanced growth inhibition in non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
KRAS mut STK11 inact mut lung adenocarcinoma sensitive MLN0128 + Phenformin Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) in combination with phenformin induced apoptosis and energetic stress in human lung adenocarcinoma cell lines with concurrent KRAS and STK11 (LKB1) mutations in culture, with higher levels than either therapy as a single agent (PMID: 26574479). 26574479
KRAS mut STK11 inact mut non-small cell lung carcinoma sensitive SAR245409 Preclinical - Cell line xenograft Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring a KRAS mutation and STK11 inactivating mutation was sensitive to XL765 (SAR245409), demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in cell line xenograft models (PMID: 24634413). 24634413
KRAS mutant stomach cancer decreased response BAY1082439 Preclinical Actionable In a preclinical study, gastric cancer xenograft models harboring KRAS mutations demonstrated decreased sensitivity to BAY1082439 in culture (AACR; 2015. Abstract nr 2674). detail...
KRAS 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 (J Clin Oncol 35, 2017 (suppl; abstr 2577)). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive BMS-754807 + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, BMS-754807 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant ovarian cancer sensitive OSI-027 Preclinical - Cell line xenograft Actionable In a preclinical study, OSI-027 inhibited tumor growth in ovarian cancer cell line xenograft models harboring KRAS mutations (PMID: 21673091). 21673091
KRAS mutant lung cancer no benefit Gefitinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iressa (gefitinib) did not demonstrate synergy at inhibiting proliferation of KRAS mutant lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant Advanced Solid Tumor resistant Everolimus Clinical Study Actionable In a clinical study, KRAS mutations were associated with resistance to Afinitor (everolimus) in patients with advanced solid tumors (PMID: 20664172). 20664172
KRAS mutant non-small cell lung carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of non-small cell cancer cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
KRAS mutant non-small cell lung carcinoma sensitive Trametinib Phase I Actionable In a Phase I trial, two non-small cell lung carcinoma patients harboring a KRAS mutation demonstrated a partial response when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS mutant pancreatic ductal adenocarcinoma sensitive Danusertib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Danusertib (PHA-739358) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant pancreatic ductal adenocarcinoma sensitive Pictilisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Pictilisib (GDC-0941) and Selumetinib (AZD6244) synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a clinical study, KRAS mutations were associated with resistance to Tarceva (erlotinib) in patients with lung adenocarcinoma (PMID: 15696205). 15696205
KRAS mutant non-small cell lung carcinoma predicted - sensitive Erlotinib + IRX4204 Preclinical - Cell culture Actionable In a preclinical study, the combination of Tarceva (erlotinib) and IRX4204 inhibited proliferation of non-small cell lung cancer cell lines in culture, including cell lines harboring KRAS mutations, and resulted in increased inhibition of proliferation and Src, p-AKT, and ribosomal S6 compared to either agent alone (J Clin Oncol 35, 2017 (suppl; abstr e14095)). detail...
KRAS mutant pancreatic cancer predicted - sensitive GI-4000 Phase I Actionable In a Phase I clinical trial, GI-4000 was well-tolerated and led to some RAS-directed immune response in patients with RAS-mutant pancreatic cancer (PMID: 25585100). 24372276 25585100
KRAS mutant colorectal cancer sensitive Reolysin Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring a KRAS mutation demonstrated growth inhibition, cell membrane dysruption, induction of apoptosis, and G2/M arrest in culture when treated with Reolysin (pelareorep) (PMID: 24798549). 24798549
KRAS mutant Advanced Solid Tumor sensitive Alpelisib + Binimetinib Phase Ib/II Actionable In a Phase Ib study, Alpelisib (BYL719) in combination with Binimetinib (MEK162) demonstrated preliminary safety and efficacy in patients with KRAS-mutant advanced solid tumors, including patients with ovarian cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 9051). detail...
KRAS mutant colorectal cancer no benefit simtuzumab + FOLFIRI Phase II Actionable In a Phase II trial, combination of Simtuzumab (GS-6634) with FOLFIRI did not improve median progression-free survival (5.5 vs 5.8 months) or median overall survival (11.4 vs 16.3 months) compared to FOLFIRI with placebo in patients with KRAS mutant colorectal cancer (PMID: 28246207; NCT01479465). 28246207
KRAS mutant non-small cell lung carcinoma no benefit Selumetinib + Docetaxel Phase III Actionable In a Phase II trial, Selumetinib (AZD6244) in combination with Taxotere (docetaxel) did not significantly improve median progression-free survival (3.9 vs 2.8 months), median overall survival (8.7 vs 7.9 months), and overall response rate (20.1% vs 13.7%) compared to placebo in KRAS-mutant non-small cell lung cancer patients (PMID: 28492898). 28492898
KRAS mutant non-small cell lung carcinoma no benefit Selumetinib + Docetaxel Phase II Actionable In a Phase II trial, Selumetinib (AZD6244) in combination with Taxotere (docetaxel) improved progression-free survival in KRAS-mutant non-small cell lung cancer patients (PMID: 23200175). 23200175
KRAS mutant breast cancer decreased response PI-273 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines harboring RAS mutations, including KRAS-mutant cell lines, demonstrated decreased sensitivity to growth inhibition by PI-273 in culture (PMID: 28827373). 28827373
KRAS mutant pancreatic ductal adenocarcinoma sensitive Nilotinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Tasigna (nilotinib) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant pancreatic cancer decreased response Pictilisib Preclinical - Cell line xenograft Actionable In a preclinical study, Pictilisib (GDC-0941) demonstrated limited efficacy as a single agent in pancreatic cell line xenograft models harboring KRAS mutations (PMID: 22952903). 22952903
KRAS mutant colorectal cancer predicted - sensitive Atezolizumab + Cobimetinib Phase I Actionable In a Phase Ib trial, Tecentriq (atezolizumab) and Cotellic (cobimetinib) combination treatment resulted in partial response in 17% (4/23) and stable disease in 22% (5/23) of colorectal cancer patients harboring KRAS mutations (Ann Oncol (2016) 27 (suppl 2): ii140). detail...
KRAS mutant Advanced Solid Tumor no benefit MLN1117 Preclinical Actionable In a preclinical study, MLN1117 (INK1117) did not inhibit tumor growth in xenograft models harboring mutations in KRAS (American Association for Cancer Research; 2011:Abstract nr 4501). detail...
KRAS mutant Advanced Solid Tumor sensitive NS1 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a KRAS mutation demonstrated sensitivity to NS1 in culture, resulting in decreased Mapk and Akt signaling and inhibition of cell transformation (PMID: 27820802). 27820802
KRAS mutant urinary bladder 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 KRAS mutant bladder cancer (PMID: 26140595). 26140595
KRAS mutant lung carcinoma sensitive AZD4785 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD4785 inhibited Kras expression, resulted in growth inhibition in 3-D cultures of lung carcinoma cell lines harboring KRAS mutations, and anti-tumor activity in cell line xenograft models (PMID: 28615361). 28615361
KRAS mutant Advanced Solid Tumor predicted - sensitive APS-2-79 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of APS-2-49 and Mekinist (trametinib) worked synergistically to decrease viability of several KRAS mutant cancer cell lines in culture (PMID: 27556948). 27556948
KRAS mutant non-small cell lung carcinoma sensitive SH-1242 Preclinical Actionable In a preclinical study, SH-1242 inhibited growth of non-small cell lung cancer cells expressing mutant KRAS in culture (PMID: 26645561). 26645561
KRAS mutant non-small cell lung carcinoma no benefit Erlotinib + MK2206 Phase II Actionable In a Phase II trial, Tarceva (erlotinib) and MK2206 combination treatment resulted in comparable 8-week disease control rate in KRAS wild-type (57%, 16/28) and KRAS mutated (25%, 2/8) patients with advanced non-small cell lung carcinoma (PMID: 27480147). 27480147
KRAS mutant lung adenocarcinoma sensitive AT13148 Preclinical Actionable In a preclinical study, AT13148 inhibited tumor growth in a human lung adenocarcinoma cell line xenograft model harboring mutant KRAS (PMID: 22781553). 22781553
KRAS mutant non-small cell lung carcinoma predicted - sensitive Paclitaxel + TVB-2640 Phase I Actionable In a Phase I trial, TVB-2640 and Taxol (paclitaxel) combination treatment resulted in partial response in 33% (1/3) and stable disease for more than 21 weeks in 67% (2/3) of patients with non-small cell lung carcinoma harboring KRAS mutations (J Clin Oncol 34, 2016 (suppl; abstr 2512)). detail...
KRAS 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 KRAS-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant pancreatic ductal carcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human pancreatic ductal carcinoma cell lines harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
KRAS mutant gastric adenocarcinoma conflicting Trametinib Preclinical Actionable In a preclinical study, the effect of Mekinist (trametinib) on human gastric adenocarcinoma cell lines harboring mutant KRAS is conflicting as cell lines were both sensitive and insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
KRAS mutant colorectal cancer predicted - sensitive Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival (PFS) of 1.5 months and overall survival (OS) of 4.7 months when dosed at 45mg, and PFS of 3.5 months and OS of 9.1 months when dosed at 60mg, in colorectal cancer patients harboring KRAS mutations (PMID: 28152546). 28152546
KRAS mutant pancreatic ductal adenocarcinoma sensitive OSI-027 + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, OSI-027 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma sensitive Selumetinib + SHP099 Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring a KRAS mutation was sensitive to the combination treatment of Selumetinib (AZD6244) and SHP099, demonstrating reduced cell viability and decreased colony formation in culture compared to either agent alone (PMID: 30045908). 30045908
KRAS mutant stomach cancer sensitive BKM120 + AG490 Preclinical Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Tyrphostin B42 (AG-490) worked synergistically to inhibit proliferation and induce apoptosis in gastric cancer cell lines harboring KRAS mutations in culture (PMID: 22159814). 22159814
KRAS mutant lung cancer sensitive Crizotinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) and Xalkori (crizotinib) demonstrated additive effect at inhibiting proliferation of KRAS mutant lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant non-small cell lung carcinoma sensitive HM95573 Preclinical - Cell line xenograft Actionable In a preclinical study, HM95573 inhibited growth of KRAS mutant non-small cell lung cancer cells in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
KRAS mutant Advanced Solid Tumor no benefit CH5132799 Preclinical Actionable In a preclinical study, human tumor cell lines harboring KRAS mutations did not demonstrate sensitivity to CH5132799 in culture (PMID: 22159814). 22159814
KRAS mutant endometrial cancer no benefit Temsirolimus Phase II Actionable In a retrospective study of a Phase II trial, mutation status of KRAS was not associated with progression-free survival or response rate in advanced endometrial cancer patients treated with Torisel (temsirolimus) (PMID: 27016228). 27016228
KRAS mutant non-small cell lung carcinoma predicted - sensitive Pembrolizumab Phase I Actionable In a clinical study, a retrospective analysis of a Phase I trial demonstrated non-small cell lung carcinoma (NSCLC) patients harboring either a TP53 mutation (n=15) or KRAS mutation (n=8) had greater progression free survival compared to NSCLC patients harboring wild-type TP53 or KRAS (n=15) (14.5mo vs 14.7mo vs 3.5mo, respectively) when treated with Keytruda (pembrolizumab) (PMID: 28039262). 28039262
KRAS mutant non-small cell lung carcinoma predicted - sensitive Pembrolizumab Clinical Study Actionable In a meta-analysis, compared to Taxotere (docetaxel), treatment with check point inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), or Tecentriq (atezolizumab), resulted in prolonged overall survival in KRAS mutant (HR=0.65, P=0.03) but not KRAS wild-type (HR=0.86, P?=?0.24) non-small cell lung carcinoma patients (PMID: 29270615). 29270615
KRAS mutant thyroid cancer sensitive HM95573 Preclinical - Cell culture Actionable In a preclinical study, HM95573 inhibited growth of KRAS mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
KRAS mutant lung squamous cell carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of squamous cell lung carcinoma cells harboring mutant KRAS in culture (PMID: 26343583). 26343583
KRAS mutant colorectal cancer sensitive HM95573 Preclinical - Cell line xenograft Actionable In a preclinical study, HM95573 inhibited growth of KRAS mutant colorectal cancer cells in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Neratinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) and Selumetinib (AZD6244) synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS 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 KRAS mutations in culture and in cell line xenograft models (PMID: 26140595). 26140595
KRAS mutant pancreatic cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) synergistically inhibited proliferation of KRAS mutant pancreatic cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant non-small cell lung carcinoma predicted - sensitive Atezolizumab Clinical Study Actionable In a meta-analysis, compared to Taxotere (docetaxel), treatment with check point inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), or Tecentriq (atezolizumab), resulted in prolonged overall survival in KRAS mutant (HR=0.65, P=0.03) but not KRAS wild-type (HR=0.86, P?=?0.24) non-small cell lung carcinoma patients (PMID: 29270615). 29270615
KRAS mutant pancreatic ductal adenocarcinoma sensitive SCH772984 Preclinical - Pdx Actionable In a preclinical study, SCH772984 inhibited tumor growth in both cell line and patient-derived xenograft models of KRAS mutant pancreatic ductal adenocarcinoma through down-regulation of Myc protein level (PMID: 26725216). 26725216
KRAS mutant colorectal cancer sensitive DEL-22379 Preclinical Actionable In a preclinical study, DEL-22379 induced tumor regression in colorectal cancer xenograft models harboring mutant KRAS (PMID: 26267534). 26267534
KRAS mutant melanoma predicted - sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 inhibited growth of RAS mutant melanoma and colorectal cancer cell lines in culture (Mol Cancer Ther November 2013 12; C146). detail...
KRAS mutant lung adenocarcinoma sensitive GI-4000 Phase II Actionable In a Phase II clinical trial, GI-4000 was well-tolerated and resulted in some immune response to KRAS in lung adenocarcinoma patients carrying KRAS mutations (PMID: 25044103). 25044103 24372276
KRAS mutant non-small cell lung carcinoma not applicable N/A Guideline Prognostic KRAS mutations are associated with shorter survival in patients with non-small cell lung carcinoma (NCCN.org). detail...
KRAS mutant colorectal cancer predicted - sensitive Ixabepilone + Sunitinib Phase I Actionable In a Phase I trial, Ixabepilone and Sutent (sunitinib) combination therapy resulted in an overall clinical benefit rate (complete response, partial response, or stable disease) of 53% (9/17) in colorectal cancer patients, most of whom harbored KRAS mutations (PMID: 26864210). 26864210
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in comparable 8-week disease control rate in KRAS wild-type (47%, 20/43) and KRAS mutated (44%, 8/18) patients with advanced non-small cell lung carcinoma (PMID: 27480147). 27480147
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase III Actionable In a Phase III trial, treatment with Nexavar (sorafenib) resulted in a longer progression free survival in patients with KRAS-mutant non-small cell lung cancer when compared to placebo, however, overall survival was similar between the two arms (PMID: 26743856). 26743856
KRAS mutant non-small cell lung carcinoma sensitive Sorafenib Phase II Actionable In a Phase II trial, treatment with Nexavar (sorafenib) resulted in partial response in 8.8% (5/57) and stable disease in 43.8% (25/57) of patients with KRAS-mutant non-small cell lung cancer (PMID: 23224737). 23224737
KRAS mutant non-small cell lung carcinoma predicted - sensitive Docetaxel + Trametinib Phase I Actionable In a Phase I/Ib trial, treatment with the combination of Mekinist (trametinib) and Taxotere (docetaxel) resulted in an overall response rate (ORR) of 24% (6/25, all partial responses), and stable disease in 36% (9/25) in the subset of patients with KRAS-mutant non-small cell lung cancer, compared to an ORR of 18% (4/22) in patients with wild-type or unknown KRAS status (PMID: 27876675). 27876675
KRAS mutant pancreatic ductal adenocarcinoma sensitive SCH772984 + Temsirolimus Preclinical - Cell culture Actionable In a preclinical study, Torisel (temsirolimus) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS 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
KRAS mutant pancreatic ductal adenocarcinoma sensitive Ralimetinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Ralimetinib (LY2228820) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring KRAS mutations were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). 19276360
KRAS mutant pancreatic adenocarcinoma predicted - sensitive PF3644022 + PF-477736 Preclinical - Patient cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 combination treatment resulted in significant apoptosis in primary tumor cells isolated from pancreas adenocarcinoma patients harboring KRAS mutations in culture (PMID: 26140595). 26140595
KRAS mutant colorectal adenocarcinoma no benefit Dasatinib + FOLFOX Phase Ib/II Actionable In a Phase Ib/II trial, the combination of Sprycel (dasatinib) and FOLFOX demonstrated minimal clinical benefit in patients with metastatic colorectal adenocarcinoma harboring KRAS codon 12/13 mutations, with no responses and a median time to treatment failure of 2.0 months (PMID: 28280091; NCT00501410). 28280091
KRAS mutant multiple myeloma resistant Trametinib Preclinical Actionable In a preclinical study, human multiple myeloma cells harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
KRAS mutant non-small cell lung carcinoma predicted - sensitive TVB-2640 Phase I Actionable In a Phase I trial, TVB-2640 treatment resulted in stable disease for more than 17 weeks in 100% (3/3) of patients with non-small cell lung carcinoma harboring KRAS mutations (J Clin Oncol 34, 2016 (suppl; abstr 2512)). detail...
KRAS mutant stomach cancer resistant Poziotinib Preclinical Actionable In a preclinical study, a human gastric cancer cell line harboring a KRAS mutation demonstrated resistance to Poziotinib (PMID: 21306821). 21306821
KRAS mutant pancreatic ductal adenocarcinoma predicted - sensitive BEZ235 + PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, the addition of PD-0325901 to treatment with BEZ235 inhibited BEZ235-enhanced ERK activation, and the combination resulted in increased inhibition of cell proliferation in KRAS-mutant pancreatic ductal adenocarcinoma cell lines in culture compared to either agent alone (PMID: 25673820). 25673820
KRAS 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 KRAS mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). 28611205
KRAS mutant colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical case report, an acquired KRAS mutation was associated with resistance to Erbitux (cetuximab) in a patient with metastatic colorectal cancer (PMID: 24304820). 24304820
KRAS mutant colorectal cancer resistant Cetuximab Clinical Study Actionable In a clinical study, KRAS mutations were associated with resistance to Erbitux (cetuximab) in patients with colorectal cancer (PMID: 18202412). 18202412
KRAS mutant colorectal cancer predicted - resistant SHP099 Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring KRAS mutations demonstrated resistance to SHP099 in culture (PMID: 27362227). 27362227
KRAS mutant colorectal cancer sensitive SAR245409 + Pimasertib Phase Ib/II Actionable In a Phase Ib trial, XL765 (SAR245409) in combination with, Pimasertib (MSC1936369B), demonstrated safety and preliminary efficacy in Kras mutant colorectal patients (Cancer Res 2013;73(8 Suppl):Abstract nr LB-147). detail...
KRAS mutant non-small cell lung carcinoma sensitive Aurora Kinase Inhibitor II Preclinical - Cell culture Actionable In a preclinical study, Aurora Kinase Inhibitor II (AI II) induced apoptosis and inhibited growth of KRAS-mutant non-small cell lung cancer cell lines in culture (PMID: 26842935). 26842935
KRAS mutant pancreatic adenocarcinoma sensitive BI-847325 Preclinical Actionable In a preclinical study, BI-847325 promoted tumor regression in mutant KRAS pancreatic adenocarcinoma models (Cancer Res 2012;72(8 Suppl):Abstract nr 1919). detail...
KRAS mutant lung cancer sensitive AZD4547 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and AZD4547 synergistically inhibited proliferation of KRAS mutant lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant pancreatic ductal adenocarcinoma sensitive Linsitinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Linsitinib (OSI-906) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant lung adenocarcinoma decreased response Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS mutations due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS mutant Advanced Solid Tumor resistant AZD8835 Preclinical Actionable In a preclinical study, tumor cell lines harboring KRAS mutations were resistant to AZD8835 induced growth inhibition in culture (PMID: 26839307). 26839307
KRAS mutant Advanced Solid Tumor sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) reduced tumor formation in 36% (8/22) of solid tumor patients harboring KRAS mutations (PMID: 22805291). 22805291
KRAS mutant pancreatic cancer predicted - sensitive Trametinib Phase I Actionable In a Phase I trial, a pancreatic cancer patient harboring a KRAS mutation demonstrated a partial response when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS mutant colon cancer predicted - sensitive OPB-111077 Phase I Actionable In a Phase I trial, a patient with colon cancer harboring a KRAS mutation demonstrated stable disease when treated with OPB-111077 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B118). detail...
KRAS mutant non-small cell lung carcinoma sensitive RO4987655 Phase I Actionable In a Phase I trial, 11% (2/11) of NSCLC patients with Kras mutations achieved partial response after treatment with RO4987655 (PMID: 24947927). 24947927
KRAS mutant hepatocellular carcinoma sensitive Refametinib + Sorafenib Phase II Actionable In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). 29950351
KRAS mutant hepatocellular carcinoma sensitive Refametinib + Sorafenib Phase II Actionable In a Phase II trial, Refametinib (BAY86-9766), in combination with Nexavar (sorafenib), demonstrated more clinical benefit in hepatocellular carcinoma patients with mutant Kras than in patients with wild-type Kras (PMID: 25294897). 25294897
KRAS mutant pancreatic 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 KRAS mutant pancreatic cancer (PMID: 26140595). 26140595
KRAS mutant colon cancer sensitive AZ-TAK1 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of AZ-TAK1 and Selumetinib (AZD6244) resulted in an additive effect in colon cancer cells harboring KRAS mutant in culture, demonstrating a 90% growth reduction (PMID: 27655129). 27655129
KRAS mutant lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a majority (12/17) lung adenocarcinoma cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
KRAS mutant 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 a KRAS mutation in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). 19018267
KRAS mutant endometrial cancer resistant Trametinib Preclinical Actionable In a preclinical study, human endometrial cancer cells harboring mutant KRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
KRAS mutant colorectal cancer predicted - sensitive Necitumumab + FOLFOX Phase II Actionable In a Phase II clinical trial, the combination of Portrazza (necitumumab) and FOLFOX in colorectal cancer patients resulted in an objective response rate (ORR) of 63.6% (28/44) in the overall intent-to-treat population, with an ORR of 56.5% (5/9; all partial responses), and stable disease in 44.4% (4/9) of KRAS-mutant patients (PMID: 26766738). 26766738
KRAS mutant pancreatic ductal adenocarcinoma sensitive PF-04691502 + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, PF-04691502 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant lung cancer sensitive BGJ398 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and BGJ398 synergistically inhibited proliferation of KRAS mutant lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant non-small cell lung carcinoma predicted - sensitive Pemetrexed + GSK1120212 Phase I Actionable In a Phase I/Ib trial, treatment with the combination of Mekinist (trametinib) and Alimta (pemetrexed) resulted in an overall response rate (ORR) of 17% (4/23, all partial responses), and stable disease in 48% (11/23) in the subset of patients with KRAS-mutant non-small cell lung cancer, compared to an ORR of 11% (2/19) in patients with wild-type or unknown KRAS status (PMID: 27876675). 27876675
KRAS mutant pancreatic ductal adenocarcinoma sensitive Navitoclax + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Navitoclax (ABT-263) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma no benefit Erlotinib Guideline Actionable KRAS mutations are associated with lack of efficacy with EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) in patients with non-small cell lung cancer (NCCN.org). detail...
KRAS mutant non-small cell lung carcinoma no benefit Erlotinib Phase II Actionable In a Phase II trial, Tarceva (erlotinib) treatment resulted in comparable 8-week disease control rate in KRAS wild-type (36%, 5/14) and KRAS mutated (20%, 1/5) patients with advanced non-small cell lung carcinoma (PMID: 27480147). 27480147
KRAS mutant pancreatic ductal adenocarcinoma sensitive Ridaforolimus + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Ridaforolimus (MK-8669) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant pancreatic ductal adenocarcinoma sensitive SCH772984 + Vistusertib Preclinical - Cell culture Actionable In a preclinical study, Vistusertib (AZD2014) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma no benefit Carboplatin + Erlotinib + Paclitaxel Phase III Actionable In a Phase III trial, the combination therapy of Tarceva (erlotinib), Paraplatin (carboplatin), and Taxol (paclitaxel) resulted in a worse overall response rate (8%) compared to Paraplatin (carboplatin) and Taxol (paclitaxel) without Tarceva (erlotinib) (23%) in non-small cell lung cancer patients harboring KRAS mutations (PMID: 16043828). 16043828
KRAS mutant non-small cell lung carcinoma no benefit Osimertinib Guideline Actionable KRAS mutations are associated with lack of efficacy with EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) in patients with non-small cell lung cancer (NCCN.org). detail...
KRAS mutant colorectal cancer sensitive Ramucirumab + FOLFIRI Phase III Actionable In a Phase III trial, Cyramza (ramucirumab) followed by FOLFIRI was equally efficacious in metastatic colorectal carcinoma patients with Kras exon 2 mutations as patients with wild-type Kras (PMID: 25877855). 25877855
KRAS mutant non-small cell lung carcinoma sensitive BI2536 Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring a KRAS mutation were more sensitive to BI2536 than cells wild-type for KRAS (PMID: 26597303). 26597303
KRAS mutant non-small cell lung carcinoma predicted - sensitive XMT-1536 Preclinical - Pdx Actionable In a preclinical study, XMT-1536 induced tumor regression in patient-derived-xenograft models of of non-small cell lung cancer harboring KRAS mutations (Proceedings of AACR, Vol 57, Apr 2016, Abstract # 1194). detail...
KRAS mutant non-small cell lung carcinoma no benefit MK2206 + Selumetinib Phase II Actionable In a Phase II trial, Selumetinib (AZD6244) and MK2206 combination treatment resulted in comparable 8-week disease control rate in KRAS wild-type (49%, 24/49) and KRAS mutated (62%, 13/21) patients with advanced non-small cell lung carcinoma (PMID: 27480147). 27480147
KRAS mutant non-small cell lung carcinoma predicted - sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 non-small cell lung carcinoma patient harboring KRAS mutation, who remained on treatment for over 572 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Panobinostat + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Farydak (panobinostat) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant thyroid medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (47 vs 8 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RAS mutations (PMID: 27525386). 27525386
KRAS mutant pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a majority (4/5) of human pancreatic adenocarcinoma cell lines harboring mutant KRAS in culture (PMID: 26343583). 26343583
KRAS mutant Advanced Solid Tumor sensitive GDC-0623 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC-0623 demonstrated efficacy in several human tumor cell line xenograft models harboring KRAS mutations (PMID: 23934108). 23934108
KRAS mutant non-small cell lung carcinoma sensitive Abemaciclib Phase I Actionable In a Phase I trial, treatment with Abemaciclib (LY2835219) in non-small cell lung carcinoma patients harboring a KRAS mutation resulted in a disease control rate of 55% (16/29) and a median PFS of 2.8 months (LY2835219) (PMID: 27217383). 27217383
KRAS mutant colon cancer decreased response Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) combination treatment was less efficient at inhibiting proliferation of KRAS mutant colon cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant pancreatic ductal adenocarcinoma sensitive PD-0325901 + Gedatolisib Preclinical - Cell culture Actionable In a preclinical study, the addition of combination PD-0325901 to treatment with Gedatolisib (PF-05212384) and PD-0325901 inhibited Gedatolisib (PF-05212384)-enhanced ERK activation, and the combination resulted in decreased proliferation of pancreatic ductal adenocarcinoma cell lines harboring KRAS mutations in culture (PMID: 25673820). 25673820
KRAS mutant pancreatic ductal adenocarcinoma sensitive AZD8186 + Ulixertinib Preclinical - Patient cell culture Actionable In a preclinical study, AZD8186 and BVD-523 synergistically inhibited growth of both established and patient-derived, SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture, and inhibited tumor growth in cell line xenograft models (PMID: 26725216). 26725216
KRAS mutant pancreatic ductal adenocarcinoma sensitive MK2206 + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, MK2206 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 resulted in a disease control rate of 11.4% (5/44) in KRAS mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). 28611205
KRAS mutant non-small cell lung carcinoma predicted - sensitive PF-04691502 Preclinical - Cell line xenograft Actionable In a preclinical study, PF-04691502 resulted in tumor regression in KRAS-mutant non-small cell lung cancer cell line xenograft models (PMID: 21750219). 21750219
KRAS mutant Advanced Solid Tumor predicted - sensitive Gedatolisib Preclinical - Cell culture Actionable In a preclinical study, Gedatolisib (PF-05212384) inhibited growth of several human solid tumor cell lines in culture, including cell lines harboring KRAS mutations (PMID: 21325073). 21325073
KRAS mutant non-small cell lung carcinoma sensitive KPT-185 Preclinical - Cell culture Actionable In a preclinical study, KPT-185 resulted in greater apoptotic activity and decreased cell viability in non-small cell lung cancer (NSCLC) cell lines harboring KRAS mutations compared to NSCLC cell lines with wild-type KRAS, suggesting a synthetic lethal effect via XPO1 inhibition (PMID: 27680702). 27680702
KRAS mutant pancreatic ductal adenocarcinoma sensitive Dinaciclib + MK2206 Preclinical - Pdx Actionable In a preclinical study, the combination of Dinaciclib (SCH 727965) and MK-2206 inhibited tumor growth and metastasis in KRAS-mutant patient-derived xenograft models of pancreatic ductal adenocarcinoma, with some models achieving complete response (PMID: 25931518). 25931518
KRAS mutant pancreatic cancer sensitive GDC-0980 + PD-0325901 Preclinical Actionable In a preclinical study, the addition of PD-0325901 to treatment with GDC-0980 and inhibited GDC-0980-enhanced ERK activation, and the combination resulted in decreased proliferation of pancreatic cancer cells harboring KRAS mutations in culture (PMID: 25673820). 25673820
KRAS mutant Advanced Solid Tumor sensitive BI-847325 Phase I Actionable In a Phase I trial, BI-847325 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including patients harboring KRAS mutations (Mol Cancer Ther 2013;12(11 Suppl):B281). detail...
KRAS mutant pancreatic cancer sensitive Pictilisib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Pictilisib (GDC-0941) and Selumetinib (AZD6244) worked synergistically to induce tumor regression in pancreatic cancer cell line xenograft models harboring KRAS mutations (PMID: 22952903). 22952903
KRAS mutant pancreatic cancer no benefit Rigosertib + Gemcitabine Phase II Actionable In a Phase II study, Estybon (rigosertib) in combination with, gemcitabine, did not demonstrate increased efficacy over gemcitabine alone and there was no correlation of reponse with Kras mutational status in pancreatic patients (PMID: 26091808). 26091808
KRAS 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 KRAS-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS 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 KRAS-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Saracatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Saracatinib (AZD0530) and Selumetinib (AZD6244) synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma sensitive Panulisib Preclinical - Cell line xenograft Actionable In a preclinical study, Panulisib (P7170) demonstrated inhibition of tumor growth in cell line xenograft models of non-small cell lung cancer harboring KRAS mutations (Cancer Res 2012, 72(8 Suppl), Abstract #3759). detail...
KRAS mutant colon cancer resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, colon cancer cells harboring KRAS mutations were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). 19276360
KRAS mutant endometrial cancer predicted - sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 endometrial cancer patient harboring harboring KRAS mutation, who remained on treatment for over 456 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
KRAS 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 KRAS-mutant non-small cell lung cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS mutant Advanced Solid Tumor sensitive CUDC-907 Preclinical - Cell line xenograft Actionable In a preclinical study, CUDC-907 induced apoptosis and cell cycle arrest in several human solid tumor and hematological cancer cell lines in culture and inhibited tumor growth in tumor cell line xenograft models, including those harboring KRAS mutations (PMID: 22693356). 22693356
KRAS 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 KRAS mutant colon cancer (PMID: 26140595). 26140595
KRAS 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...
KRAS mutant lung cancer no benefit Afatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Gilotrif (afatinib) did not demonstrate synergy at inhibiting proliferation of KRAS mutant lung cancer cells in culture (PMID: 27338794). 27338794
KRAS mutant lung adenocarcinoma decreased response Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) only moderately inhibited survival of lung adenocarcinoma cells harboring KRAS mutations due to the adaptive activation of Met, Egfr, and Akt signaling in cells (PMID: 27422710). 27422710
KRAS mutant lung cancer sensitive Ponatinib + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) and Iclusig (ponatinib) synergistically inhibited proliferation of KRAS mutant lung cancer cells in culture and induced tumor regression in xenograft models (PMID: 27338794). 27338794
KRAS 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 KRAS-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS mutant colorectal cancer sensitive Irinotecan + Reolysin Preclinical - Cell culture Actionable In a preclinical study, the combination of Reolysin (pelareorep) and Camptosar (irinotecan) resulted in a synergistic effect, demonstrating increased apoptotic activity and growth inhibition in colorectal cancer cells harboring a KRAS mutation in culture compared to either agent alone (PMID: 24798549). 24798549
KRAS mutant colorectal cancer sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 inhibited growth of colorectal cancer cells harboring KRAS mutations in culture and in xenograft models (PMID: 23475782). 23475782
KRAS mutant lung cancer predicted - sensitive DT-061 Preclinical - Pdx & cell culture Actionable In a preclinical study, the small-molecule activators of PP2A (SMAP) DT-061 inhibited Mapk signaling, resulted in growth inhibition and apoptosis in KRAS mutant lung cancer cell lines in culture, and in both cell line and patient-derived xenograft models (PMID: 28504649). 28504649
KRAS mutant lung adenocarcinoma predicted - sensitive PF3644022 + PF-477736 Preclinical - Patient cell culture Actionable In a preclinical study, primary tumor cells isolated from lung adenocarcinoma patients harboring KRAS mutations demonstrated increased sensitivity to Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 combination treatment in culture compared to cells lacking KRAS or BRAF mutations (PMID: 26140595). 26140595
KRAS mutant Advanced Solid Tumor predicted - 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...
KRAS mutant gastric adenocarcinoma sensitive Selumetinib Preclinical Actionable In a preclinical study, gastric cancer cell lines with Kras mutations were sensitive to Selumetinib (AZD6244) (PMID: 24935174). 24935174
KRAS mutant Advanced Solid Tumor predicted - sensitive Cobimetinib + GDC-0068 Phase I Actionable In a Phase I trial, the combination of Ipatasertib (GDC-0068) and Cobimetinib (GDC-0973) demonstrated safety and preliminary efficacy in patients with advanced solid tumors, including patients harboring KRAS mutations (Cancer Res, October 1, 2014 74; CT328). detail...
KRAS mutant colorectal cancer sensitive Palbociclib + Trametinib Preclinical - Pdx Actionable In a preclinical study, Mekinist (trametinib) and Ibrance (palbociclib) combination treatment resulted in objective response in PDX models of colorectal cancer cells harboring KRAS mutations (PMID: 26369631). 26369631
KRAS mutant pancreatic ductal adenocarcinoma sensitive Everolimus + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, AZD8186 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant Advanced Solid Tumor sensitive MK2206 + Romidepsin Preclinical Actionable In a preclinical study, treatment with the combination of MK2206 and Istodax (romidepsin) resulted in greater cell death in tumor cell lines harboring Kras mutations compared to cell lines with wild-type Kras (Cancer Res April 15, 2012 72:4708) detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Saracatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Saracatinib (AZD0530) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant Advanced Solid Tumor sensitive RAF709 Phase I Actionable In a preclinical study, cancer cell lines harboring KRAS mutations demonstrated increased sensitivity to RAF709 compared to KRAS wild-type cells in culture (PMID: 29343524). 29343524
KRAS mutant colon cancer sensitive AZ-TAK1 Preclinical - Cell culture Actionable In a preclinical study, a colon cancer cell line harboring a KRAS mutation demonstrated sensitivity to AZ-TAK1 in culture, resulting in a 50% cell growth reduction (PMID: 27655129). 27655129
KRAS mutant non-small cell lung carcinoma sensitive Volasertib Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring a KRAS mutation were more sensitive to volasertib than cells wild-type for KRAS (PMID: 26597303). 26597303
KRAS mutant lung adenocarcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study Actionable In a clinical study, lung adenocarcinoma patients harboring a KRAS mutation demonstrated an intermediate objective response rate (28.6% vs 35.7% vs 7.4%) compared to patients with co-occurring KRAS and TP53 mutations and patients with co-occurring KRAS and STK11 mutations when treated with a PD-1 inhibitor (Nivolumab, n=146; Pembrolizumab, n=19) (PMID: 29773717). 29773717
KRAS mutant pancreatic ductal adenocarcinoma sensitive AZD8186 + SCH772984 Preclinical - Pdx & cell culture Actionable In a preclinical study, AZD8186 and SCH772984 synergistically inhibited growth of both established and patient-derived, SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant colorectal cancer no benefit RO4987655 Phase I Actionable In a Phase I trial, none of 30 colorectal cancer patients with KRAS mutations achieved favorable response after treatment with RO4987655 (PMID: 24947927). 24947927
KRAS mutant colorectal cancer no benefit Cetuximab + FOLFIRI Phase III Actionable In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843). 25605843
KRAS mutant colorectal cancer no benefit Panitumumab + Oxaliplatin + Fluorouracil + Irinotecan Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with KRAS mutations (PMID: 26341920). 26341920
KRAS mutant lung 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 KRAS mutant lung cancer (PMID: 26140595). 26140595
KRAS mutant leukemia predicted - sensitive Trametinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). detail...
KRAS mutant pancreatic ductal adenocarcinoma sensitive Midostaurin + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Clinical Study Actionable In a meta-analysis, compared to Taxotere (docetaxel), treatment with check point inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), or Tecentriq (atezolizumab), resulted in prolonged overall survival in KRAS mutant (HR=0.65, P=0.03) but not KRAS wild-type (HR=0.86, P=0.24) non-small cell lung carcinoma patients (PMID: 29270615). 29270615
KRAS mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Phase III Actionable In a Phase III trial, non-small cell lung carcinoma patients harboring a KRAS mutation demonstrated an objective response rate (ORR) of 18.2% (2/11) when treated with Opdivo (nivolumab) compared to an ORR of 57.1% (4/7) in patients co-harboring a KRAS mutation and TP53 mutation and an ORR of 0% (0/6) in patients co-harboring a KRAS mutation and STK11 mutation (PMID: 29773717; NCT01673867). 29773717
KRAS mutant Advanced Solid Tumor no benefit MEHD7945A + Cobimetinib Phase I Actionable In a Phase I trial, Duligotuzumab (MEHD7945A) and Cotellic (cobimetinib) combination therapy demonstrated limited safety and efficacy, with stable disease as best response in 41% (9/22) of patients with KRAS-mutant solid tumors (PMID: 28592615; NCT01986166). 28592615
KRAS mutant colorectal cancer predicted - sensitive Regorafenib Phase III Actionable In a Phase III trial, Stivarga (regorafenib) treatment resulted in a median progression free survival (PFS) of 2.3 months in metastatic colorectal cancer patients harboring KRAS mutations, and a median PFS of 2.1 months in KRAS wild-type patients (J Clin Oncol 34, 2016 (suppl 4S; abstr 735), NCT01001377). detail...
KRAS mutant colon adenocarcinoma not applicable N/A Phase III Emerging In a post-hoc analysis of a Phase III trial, KRAS 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 KRAS mutations may serve as a future prognostic biomarker in this patient population (PMID: 26768652). 26768652
KRAS 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 KRAS-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
KRAS mutant ovarian cancer sensitive Alpelisib + Binimetinib Phase I Actionable In a Phase I clinical trial, Alpelisib (BYL719), in combination with Binimetinib (MEK162), demonstrated safety and preliminary efficacy in patients with KRAS-mutant advanced solid tumors, including patients with ovarian cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 9051). detail...
KRAS mutant non-small cell lung carcinoma no benefit Gefitinib Guideline Actionable KRAS mutations are associated with lack of efficacy with EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) in patients with non-small cell lung cancer (NCCN.org). detail...
KRAS mutant Advanced Solid Tumor sensitive Metformin Preclinical - Cell line xenograft Actionable In a preclinical study, Glucophage (metformin) inhibited tumor growth in a variety of KRAS-mutant cancer cell line xenograft models (PMID: 23877793). 23877793
KRAS mutant colorectal cancer sensitive CI-1040 Preclinical Actionable In a preclinical study, colorectal cancer cells harboring KRAS mutations demonstrated sensitivity to CI-1040 in culture (PMID: 19372556). 19372556
KRAS mutant pancreatic ductal adenocarcinoma sensitive Ipatasertib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Ipatasertib (GDC-0068) and Selumetinib (AZD6244) synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant colon cancer predicted - sensitive Luminespib Preclinical - Cell line xenograft Actionable In a preclinical study, colon cancer cell lines with KRAS codon 12 or 13 mutations demonstrated increased sensitivity to treatment with Luminespib (AUY922) in culture and in xenograft models (PMID: 26832792). 26832792
KRAS mutant colorectal cancer decreased response Bevacizumab Clinical Study Actionable In a systematic review of 2,266 colorectal cancer patients, treatment with Avastin (bevacizumab) increased progression-free survival in patients harboring wild-type KRAS but not in patients with mutant KRAS (PMID: 23828442). 23828442
KRAS mutant pancreatic ductal adenocarcinoma sensitive Pictilisib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Ipatasertib (GDC-0068) and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant non-small cell lung carcinoma no benefit Afatinib Guideline Actionable KRAS mutations are associated with lack of efficacy with EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) in patients with non-small cell lung cancer (NCCN.org). detail...
KRAS mutant lung adenocarcinoma no benefit Salirasib Phase II Actionable In a Phase II clinical trial, salirasib showed no benefit in KRAS-mutant lung adenocarcinoma patients (PMID: 21847063). 21847063
KRAS mutant colorectal cancer sensitive Trametinib Phase I Actionable In a Phase I trial, of eight patients with colorectal cancer, three patients harbored a KRAS mutation and demonstrated stable disease when treated with Mekinist (trametinib) (PMID: 22805291). 22805291
KRAS mutant pancreatic ductal adenocarcinoma sensitive AZD8055 + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, AZD8055 and SCH772984 synergistically inhibited growth of SCH772984-sensitive, KRAS mutant pancreatic ductal adenocarcinoma cell lines in culture (PMID: 26725216). 26725216
KRAS mutant TP53 mutant colorectal cancer sensitive Abemaciclib Phase I Actionable In a Phase I trial, a colorectal cancer patient co-harboring a KRAS mutation and TP53 mutation demonstrated sensitivity when treated with Abemaciclib (LY2835219), which resulted in stable disease (PMID: 27217383). 27217383
KRAS mutant TP53 mutant lung adenocarcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study Actionable In a clinical study, lung adenocarcinoma patients co-harboring a KRAS mutation and TP53 mutation demonstrated a greater objective response rate (35.7% vs 7.4% vs 28.6%) compared to patients with KRAS and STK11 mutations and patients with KRAS mutations only when treated with a PD-1 inhibitor (Nivolumab, n=146; Pembrolizumab, n=19) (PMID: 29773717). 29773717
KRAS mutant TP53 mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Phase III Actionable In a Phase III trial, non-small cell lung carcinoma patients co-harboring a KRAS mutation and TP53 mutation demonstrated an objective response rate (ORR) of 57.1% (4/7) when treated with Opdivo (nivolumab) compared to an ORR of 0% (0/6) in patients co-harboring a KRAS mutation and STK11 mutation and an ORR of 18.2% (2/11) in patients with mutant KRAS only (PMID: 29773717; NCT01673867). 29773717
KRAS mutant TP53 mutant non-small cell lung carcinoma predicted - sensitive Pembrolizumab Phase I Actionable In a clinical study, a retrospective analysis of a Phase I trial demonstrated four non-small cell lung carcinoma (NSCLC) patients co-harboring a TP53 mutation and KRAS mutation had greater progression free survival compared to NSCLC patients harboring a single TP53 mutation or single KRAS mutation when treated with Keytruda (pembrolizumab) (PMID: 28039262). 28039262
KRAS mutant TP53 mutant colorectal cancer sensitive ABT-263 + Alpelisib + Erlotinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Mekinist (trametinib), Alpelisib (BYL719), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a KRAS mutation and TP53 mutation compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
FGFR1 dec exp KRAS mut colorectal cancer no benefit Trametinib Preclinical - Cell culture Actionable In a preclinical study, knocking down of Fgfr1 through shRNA did not sensitize KRAS mutant colorectal cancer cells to Mekinist (trametinib) induced growth inhibition in culture (PMID: 27338794). 27338794
FGFR1 dec exp KRAS mut pancreatic cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition of KRAS mutant pancreatic cancer cells with decreased Fgfr1 expression through shRNA knockdown in culture (PMID: 27338794). 27338794
FGFR1 dec exp KRAS mut lung cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) treatment demonstrated enhanced growth inhibition in KRAS mutant lung cancer cells with decreased Fgfr1 expression through shRNA knockdown in culture, and tumor regression in xenograft models (PMID: 27338794). 27338794
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
KRAS mutant PIK3CA E545K colon cancer sensitive BKM120 + Cetuximab Preclinical Actionable In a preclinical study, Buparlisib (BKM120) worked synergistically with Erbitux (cetuximab) to inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA E545K in culture (PMID: 26715098). 26715098
KRAS mutant PIK3CA E545K colon cancer no benefit Cetuximab Preclinical Actionable In a preclinical study, Erbitux (cetuximab) did not inhibit proliferation of colon cancer cell lines harboring mutant KRAS and PIK3CA E545K in culture (PMID: 26715098). 26715098
KRAS mutant PIK3CA E545K colon cancer decreased response Buparlisib Preclinical Actionable In a preclinical study, colon cancer cell lines harboring mutant KRAS and PIK3CA E545K demonstrated reduced sensitivity to Buparlisib (BKM120) induced growth inhibition in culture (PMID: 26715098). 26715098
KRAS G12D STK11 inact mut lung cancer sensitive Sapanisertib Preclinical Actionable In a preclinical study, Sapanisertib (MLN0128) inhibited lung tumor growth in mouse models with KRAS G12D and inactivation of STK11 (LKB1), and demonstrated limited efficacy in tumors with KRAS G12D and wild-type STK11 (PMID: 26574479). 26574479
BRAF wild-type KRAS G12D pancreatic cancer resistant GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type pancreatic cancer cells harboring KRAS G12D in cell line xenograft models (PMID: 19276360). 19276360
PIK3CA G1049R KRAS G12D PIK3CA amp endometrial cancer sensitive BEZ235 + PD98509 Preclinical Actionable In a preclinical study, the combination of BEZ235 and the MEK1 inhibitor PD98509 worked synergistically or additively to inhibit growth of endometrial cancer cells harboring PIK3CA G1049R, KRAS G12D, and amplification of PIK3CA in culture (PMID: 22662154). 22662154
KRAS G12D TP53 S127Y lung adenocarcinoma sensitive Dasatinib + Demcizumab Preclinical - Pdx Actionable In a preclinical study, combination of Sprycel (dasatinib) and Demcizumab (OMP-21M18) treatment resulted in durable tumor inhibition in patient-derived animal models of lung adenocarcinoma harboring KRAS G12D and TP53 S127Y (PMID: 26855149). 26855149
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition in culture (PMID: 27231123). 27231123
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition in culture and in xenograft models (PMID: 27231123). 27231123
KRAS G12D PTEN dec exp TP53 R306* colorectal cancer no benefit MLN0128 + PD-0325901 Preclinical - Pdx Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 combination treatment did not result in tumor growth stabilization in patient-derived xenograft models of colorectal cancer harboring KRAS G12D, decreased PTEN expression, and TP53 R306* (PMID: 26272063). 26272063
APC inact mut KRAS G12D PTEN inact mut colorectal cancer sensitive BEZ235 + Binimetinib Preclinical Actionable In a preclinical study, combination of BEZ235 and Binimetinib (MEK162) increased survival compared to single agent in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D PTEN inact mut colorectal cancer sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 inhibited mTOR signaling in tumors and increased survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation, and KRAS G12D (PMID: 26206338). 26206338
APC inact mut KRAS G12D PTEN inact mut colorectal cancer no benefit Binimetinib Preclinical Actionable In a preclinical study, Binimetinib (MEK162) increased both apoptosis and proliferation in tumors, resulted in no improvement in survival in transgenic animal models of colorectal cancer driven by APC and PTEN inactivation and KRAS G12D (PMID: 26206338). 26206338
KRAS G12D MET amp esophageal carcinoma resistant AMG 337 Clinical Study Actionable In a clinical case study, a patient with a MET amplified esophageal carcinoma that initially responded to AMG 337, developed resistance upon emergence of KRAS G12D (PMID: 26432108). 26432108
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer decreased response Selumetinib Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) delayed tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer predicted - sensitive BEZ235 Preclinical - Pdx Actionable In a preclinical study, BEZ235 inhibited tumor growth in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
KRAS G12D PIK3CA H1047R TP53 wild-type colorectal cancer no benefit Selumetinib + BEZ235 Preclinical - Pdx Actionable In a preclinical study, Selumetinib (AZD6244) and BEZ235 combination treatment did not improve tumor growth stabilization compared to single agent in patient-derived xenograft models of TP53 wild-type colorectal cancer harboring KRAS G12D and PIK3CA H1047R (PMID: 26272063). 26272063
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive Gemcitabine + SRA737 Preclinical Actionable In a preclinical study, Gemzar (gemcitabine) resulted in enhanced antitumor efficacy, including decreased tumor volume, when combined with SRA737 (CCT245737) in a pancreatic ductal adenocarcinoma transgenic mouse model harboring KRAS G12D and TP53 R175H (PMID: 27167172). 27167172
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma conflicting Sirolimus Preclinical Actionable In a preclinical study, Rapamune (sirolimus) treatment in transgenic animal models of pancreatic ductal adenocarcinoma harboring KRAS G12D and TP53 R175H resulted in proliferation of tumor cells in interior, hypovascularized tumor regions, but inhibited proliferation in outer, vascularized tumor regions, despite inhibition of mTORC signaling in both regions (PMID: 26144316). 26144316
KRAS G12D TP53 R175H pancreatic cancer sensitive Pimasertib + Gemcitabine Preclinical Actionable In a preclinical study, the combination of pimasertib and Gemzar (gemcitabine) inhibited tumor growth in a syngeneic mouse model of pancreatic cancer expressing KRAS G12D and TP53 R175H (PMID: 26228206). 26228206
KRAS G12D TP53 R175H pancreatic ductal adenocarcinoma sensitive