Molecular Profile Detail

Profile Name BRAF G466V
Gene Variant Detail

BRAF G466V (loss of function)

Relevant Treatment Approaches MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G469R NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF G469R NRAS Q61K melanoma sensitive LY3009120 LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). 26343583
BRAF F595L Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with Zelboraf (vemurafenib) did not reduce activation of Mek and Erk by BRAF F595L in transformed cells in culture (PMID: 26582644). 26582644
BRAF D594N non-small cell lung carcinoma predicted - sensitive RMC-4550 Preclinical - Pdx Actionable In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF D594N (PMID: 30104724). 30104724
BRAF D594N Advanced Solid Tumor predicted - resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Mek in transformed cells expressing BRAF D594N in culture (PMID: 28783719). 28783719
BRAF G464E KRAS G12D melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G464E and KRAS G12D in culture (PMID: 29903896). 29903896
BRAF G464E KRAS G12D melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G464E and KRAS G12D in culture (PMID: 29903896). 29903896
BRAF G464E Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464E (PMID: 26343582). 26343582
BRAF L597R Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). 22798288
BRAF L597R Advanced Solid Tumor sensitive Vemurafenib Preclinical Actionable In a preclinical study, treatment of cells expressing BRAF L597R with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF F247L Advanced Solid Tumor sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Tafinlar (dabrafenib) in culture (PMID: 28512244). 28512244
BRAF F247L Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Mekinist (trametinib) in culture (PMID: 28512244). 28512244
BRAF L514V breast cancer resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) did not inhibit Erk and Mek signaling in breast cancer cells expressing BRAF L514V in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Tafinlar (dabrafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3245 Preclinical - Cell culture Actionable In a preclinical study, BGB3245 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response TAK-632 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to TAK-632-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E ganglioglioma resistant Dabrafenib Clinical Study Actionable In a clinical case study, a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E progressed after initial response to Tafinlar (dabrafenib) treatment, and was found to have acquired a BRAF L514V in cis with BRAF V600E, which conferred dabrafenib resistance in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response PLX8394 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3290 Preclinical - Cell culture Actionable In a preclinical study, BGB3290 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF V600E BRAF L505H melanoma resistant Vemurafenib Clinical Study Actionable In a clinical case study, a melanoma patient harboring BRAF V600E treated with Zelboraf (vemurafenib) subsequently demonstrated resistance likely due to the secondary resistance mutation, BRAF L505H (PMID: 25515853). 25515853
BRAF L505H melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). 24283590
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib FDA approved Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, which included patients identified to harbor BRAF V600E or BRAF V600K (PMID: 27480103; NCT01689519). 27480103
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). 25399551
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-AD) that supported FDA approval, adjuvant treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved estimated 3-year relapse-free survival rate (58% vs 39%, HR=0.47, P<0.001) and 3-year overall survival rate (86% vs 77%, HR=0.57; 95% CI, 0.42 to 0.79, P=0.0006) compared to placebo in stage III melanoma patients harboring BRAF V600E or V600K mutations (PMID: 28891408; NCT01682083). 28891408
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292). 22805292
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable melanoma harboring BRAF V600E or V600K mutations (NCCN.org). detail...
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). 30219628
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453). 29573941
BRAF V600E/K melanoma predicted - sensitive XL888 + Vemurafenib Phase I Actionable In a Phase I trial, combined Zelboraf (vemurafenib) and XL888 treatment in patients with unresectable, BRAF inhibitor naive, metastatic melanoma harboring BRAF V600E (n=20) or V600K (n=1) resulted in complete and partial responses in 15% (3/20) and 60% (12/20) of evaluable patients, respectively, a 9.2-month median progression free survival, and a 34.6-month overall survival (PMID: 29674508). 29674508
BRAF V600E/K PTEN loss Advanced Solid Tumor predicted - sensitive PX-866 + Vemurafenib Phase I Actionable In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). 29051322
BRAF V600R melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive Dabrafenib Clinical Study Actionable In a clinical case study, a melanoma patient harboring BRAF V600R treated with Tafinlar (dabrafenib) demonstrated a reduction in lesion size after 2.5 months and at 5 months, stable disease, however, after 7 months progression ensued (PMID: 27255157). 27255157
BRAF V600R melanoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V487_P492delinsA pancreatic cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer sensitive LY3009120 LY3009120 Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA were sensitive to LY3009120 in culture and in xenograft models, resulting in inhibition of tumor growth and partial tumor regression (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer resistant Dabrafenib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Tafinlar (dabrafenib) (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). 26732095
BRAF V600D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D pilocytic astrocytoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, single Tafinlar (dabrafenib) and subsequent Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease stablization in a patient with pilocytic astrocytoma harboring BRAF V600D (PMID: 28784858). 28784858
BRAF V600D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited MEK and ERK phosphorylation and growth of melanoma cells harboring BRAF V600D in culture (PMID: 25500121, PMID: 17210691). 25500121 17210691
BRAF V600D melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive CCT196969 Preclinical Actionable In a preclinical study, CCT196969 inhibited MEK and ERK phosphorylation and growth of melanoma cells harboring BRAF V600D in culture (PMID: 25500121, PMID: 17210691). 25500121 17210691
BRAF V600D NRAS dec exp melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600D and knockdown of NRAS demonstrated a decreased response to Mektovi (binimetinib) relative to cells without NRAS knockdown in culture (PMID: 29245078). 29245078
BRAF V600D PTEN loss melanoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600D (PMID: 25637314). 25637314
BRAF G464V KRAS G13D breast cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a breast cancer cell line harboring BRAF G464V and KRAS G13D in culture (PMID: 29903896). 29903896
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
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 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 breast cancer predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a breast cancer cell line harboring BRAF G464V and KRAS G13D in culture (PMID: 29903896). 29903896
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 no benefit Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a breast cancer cell line harboring BRAF G464V and KRAS G13D in culture (PMID: 29903896). 29903896
BRAF G464V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464V (PMID: 26343582). 26343582
BRAF G464V Advanced Solid Tumor resistant Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). 29320312
BRAF N581Y colon cancer resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, colon cancer cells harboring BRAF N581Y were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). 19276360
BRAF Y472C non-small cell lung carcinoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung carcinoma cells harboring BRAF Y472C in culture (PMID: 22649091). 22649091
BRAF V600E BRAF T529N Advanced Solid Tumor resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to PLX4720 in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor resistant RAF265 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to RAF265 in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to SB590885 in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor conflicting Sorafenib Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to Nexavar (sorafenib)-mediated inhibition of Erk phosphorylation but were equally as sensitive to Nexavar (sorafenib)-mediated growth inhibition as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529N Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). 20538618
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, Cotellic (cobimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF K601E BRAF S363F melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). 29903896
BRAF G464R Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464R (PMID: 26343582). 26343582
BRAF G466E melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF G466E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF G466E melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466E HRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). 28783719
BRAF amp BRAF V600E colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF amp BRAF V600E lung adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + SCH772984 + Trametinib Preclinical - Pdx Actionable In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable tumor inhibition in cell line xenograft models of BRAF V600E mutated lung adenocarcinoma cells that acquired resistance to Erk inhibitors through BRAF amplification (PMID: 28714990). 28714990
BRAF amp BRAF V600E lung adenocarcinoma decreased response SCH772984 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived BRAF V600E mutant lung adenocarcinoma cells that acquired resistance to Erk inhibitor through BRAF amplification were less sensitive to SCH772984 in culture (PMID: 28714990). 28714990
BRAF amp BRAF V600E colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF amp BRAF V600E colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification (PMID: 27312529). 27312529
BRAF amp BRAF V600X NRAS Q61K melanoma resistant Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF fusion pilocytic astrocytoma not applicable N/A Guideline Diagnostic BRAF fusions aid in the diagnosis of pilocytic astrocytoma (NCCN.org). detail...
BRAF fusion pilocytic astrocytoma not applicable N/A Guideline Prognostic BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (NCCN.org). detail...
BRAF N486_P490del ovarian cancer resistant Vemurafenib Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was resistant to Zelboraf (vemurafenib), resulting in minimal inhibition of both cell growth and phosphorylation of MEK and ERK in culture (PMID: 26732095). 26732095
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). 26732095
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). 29903880
BRAF N486_P490del ovarian cancer sensitive LY3009120 LY3009120 Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to LY3009120, resulting in inhibition of cell growth and decreased phosphorylation of MEK and ERK in culture (PMID: 26732095). 26732095
BRAF N486_P490del ovarian cancer predicted - resistant Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) resulted in minimal growth inhibitory activity of an ovarian cancer cell line harboring BRAF N486_P490del (PMID: 26732095). 26732095
BRAF G466V NRAS Q61K non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). 28783719
BRAF G466V non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). 28783719
BRAF G466V non-small cell lung carcinoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring BRAF G466V demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466V non-small cell lung carcinoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 27523909). 27523909
BRAF G466V lung cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of lung cancer cells harboring BRAF G466V in culture (PMID: 30104724). 30104724
BRAF G466V colorectal cancer sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer no benefit Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit ERK signaling or tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx Actionable In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). 28783719
BRAF G466V colorectal cancer predicted - sensitive Irinotecan + Panitumumab Clinical Study Actionable In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan) (PMID: 28783719). 28783719
BRAF G466V lung adenocarcinoma sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G466V in culture (PMID: 27834212). 27834212
BRAF G466V 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 BRAF G466V mutation in culture (PMID: 26090892). 26090892
BRAF G466V non-small cell lung carcinoma sensitive Dasatinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung cancer cells expressing BRAF G466V in culture (PMID: 22649091). 22649091
BRAF G466V non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 28947956). 28947956
BRAF G466V Advanced Solid Tumor no benefit Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G466V (PMID: 29320312; NCT02091141). 29320312
AKT1 E17K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 E17K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R melanoma resistant Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF V600X melanoma sensitive ASN003 Preclinical - Pdx Actionable In a preclinical study, melanoma patient derived xenograft (PDX) model harboring a BRAF V600 mutation demonstrated antitumor activity when treated with ASN003 (J Clin Oncol 35, 2017 (suppl; abstr e14102)). detail...
BRAF V600X melanoma sensitive MK2206 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib Phase III Actionable In a Phase III trial, combination treatment with Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months compared to 7.2 months with Zelboraf (vemurafenib) alone among patients with BRAF V600-mutated metastatic melanoma (PMID: 27480103; NCT01689519). 27480103
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X cholangiocarcinoma sensitive Vemurafenib Phase II Actionable In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in partial response in 12% (1/8) and stable disease in 50% (4/8) of cholangiocarcinoma patients with BRAF V600 mutations (PMID: 26287849). 26287849
BRAF V600X melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X thyroid cancer predicted - sensitive Vemurafenib Phase II Actionable In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 29% (2/7), with 1 complete response and 1 partial response, in patients with anaplastic thyroid cancer patients with BRAF V600 mutations (PMID: 26287849). 26287849
BRAF V600X colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in partial response or better in 12% (5/43), including 1 complete response, and stable disease in 51% (22/43) of patients with BRAF V600-mutant colorectal cancer (PMID: 26392102). detail... 26392102
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AMG 232 + Trametinib + Dabrafenib Phase I Actionable In a Phase I trial, the combination therapy of AMG 232, Mekinist (trametinib), and Tafinlar (dabrafenib) in 6 patients with metastatic cutaneous melanoma harboring a BRAF V600 mutation resulted in 4 patients with a partial response and 2 patients with stable disease, and of the 6 patients, all experienced tumor reduction (J Clin Oncol 35, 2017 (suppl; abstr 2575)). detail...
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BKM120 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Selumetinib (AZD6244) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor MK2206 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive BKM120 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X colorectal cancer sensitive Vemurafenib + Cetuximab Phase II Actionable In a Phase II clinical trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer (PMID: 26287849). 26287849
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BKM120 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Atezolizumab + Vemurafenib + Cobimetinib Phase Ib/II Actionable In a Phase Ib trial, the combination of Tecentriq (atezolizumab), Cotellic (cobimetinib), and Zelboraf (vemurafenib) resulted in antitumor efficacy in BRAF V600 positive melanoma patients, demonstrating an unconfirmed RECIST response in 85.3% (29/34) of patients, including 6 CRs and 23 PRs, and confirmed PRs in three patients (J Clin Oncol 35, 2017 (suppl; abstr 3063)). detail...
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 activating mutation, as adjuvant treatment for patients with Stage III disease, or as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Phase Ib/II Actionable In a Phase I/II clinical trial, patients with BRAF V600 mutant melanoma (n=78) treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) had a median overall survival of greater than 2 years (PMID: 26811525). 26811525
BRAF V600X colorectal cancer no benefit Vemurafenib Phase II Actionable In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) in colorectal cancer patients with BRAF V600 mutations did not result in clinical benefit, with no patients achieving response, and 50% (5/10) demonstrating progressive disease (PMID: 26287849). 26287849
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase II Actionable In a Phase II trial, 20% (8/41) of melanoma patients with BRAF V600 mutations had a partial response to Binimetinib (MEK162) (PMID: 23414587). 23414587
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Selumetinib (AZD6244) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
BRAF V600X colorectal cancer sensitive Vemurafenib + Cetuximab + Irinotecan Phase Ib/II Actionable In a Phase Ib trial, the addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 mo vs. 2.0 mo), and disease control rate (67% vs. 22%), compared to Camptosar (irinotecan) plus Erbitux (cetuximab) without Zelboraf (vemurafenib), in patients with BRAF V600-mutant colorectal cancer (J Clin Oncol 35, 2017 (suppl 4S; abstract 520)). detail...
BRAF V600X melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X PTEN neg melanoma sensitive GSK2141795 Preclinical - Cell culture Actionable In a preclinical study, lack of PTEN expression was associated with increased sensitivity to GSK2141795 in BRAF V600-mutant melanoma cell lines in culture (PMID: 24265152). 24265152
BRAF V600X PTEN H93D melanoma sensitive Vemurafenib Clinical Study Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation and PTEN H93D treated with Zelboraf (vemurafenib) for 66 weeks demonstrated a partial response (PMID: 24265153). 24265153
AKT1 Q79K BRAF V600X PTEN pos melanoma sensitive MK2206 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited AKT activation and growth of PTEN-expressing BRAF V600-mutant melanoma cells expressing AKT1 Q79K in culture, with increased efficacy over either agent alone (PMID: 24265152). 24265152
AKT1 Q79K BRAF V600X PTEN pos melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of AKT1 Q79K in a wild-type PTEN-expressing BRAF V600-mutant melanoma cell line conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 24265152). 24265152
BRAF L485Y non-small cell lung carcinoma resistant GDC0879 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring BRAF L485Y were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). 19276360
BRAF L597S BRAF R239Q melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) increased growth inhibition in patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 67% of tumors, increased inhibition of ERK phosphorylation, and increased tumor growth delay compared to either agent alone in a patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF L597S BRAF R239Q melanoma sensitive Encorafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and delayed tumor growth and induced shrinkage in 8% (1/12) of tumors in a melanoma patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF L597S BRAF R239Q melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a patient-derived melanoma cell line harboring BRAF L597S, as well as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 100% (13/13) of subcutaneous tumors, and decreased growth of intracranial tumors in a patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF L597S BRAF R239Q melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited growth of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and induced tumor shrinkage in 25% (3/12) of tumors and delayed tumor growth in a patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive LY3009120 LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma no benefit Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V non-small cell lung carcinoma sensitive Sorafenib Clinical Study Actionable In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions and complete response in the lung metastasis following treatment with Nexavar (sorafenib) (PMID: 27388325). 27388325
BRAF G469V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469V (PMID: 26343582). 26343582
BRAF G469V melanoma no benefit Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) did not inhibit ERK phosphorylation or proliferation of a melanoma cell line harboring BRAF G469V (PMID: 29903896). 29903896
BRAF V600K melanoma sensitive GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600K, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). 25399551
BRAF V600K melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib FDA approved Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, which included patients identified to harbor BRAF V600E or BRAF V600K (PMID: 27480103; NCT01689519). 27480103
BRAF V600K melanoma predicted - sensitive Nivolumab Clinical Study Actionable In a retrospective analysis, patients with melanoma harboring BRAF V600K (n=19) had increased tumor mutational burden and greater response rates (53% vs. 29%, p=0.059), progression-free survival (19 vs. 2.7 months, p=0.049), and overall survival (20.4 vs. 11.7 months, p=0.081) relative to patients with BRAF V600E (n=84) when treated with Keytruda (pembrolizumab) (n=17 and 62 for BRAF V600K and V600E, respectively) or Opdivo (nivolumab) (n=2 and 22 for BRAF V600K and V600E, respectively) (PMID: 30630828). 30630828
BRAF V600K melanoma predicted - sensitive Pembrolizumab Clinical Study Actionable In a retrospective analysis, patients with melanoma harboring BRAF V600K (n=19) had increased tumor mutational burden and greater response rates (53% vs. 29%, p=0.059), progression-free survival (19 vs. 2.7 months, p=0.049), and overall survival (20.4 vs. 11.7 months, p=0.081) relative to patients with BRAF V600E (n=84) when treated with Keytruda (pembrolizumab) (n=17 and 62 for BRAF V600K and V600E, respectively) or Opdivo (nivolumab) (n=2 and 22 for BRAF V600K and V600E, respectively) (PMID: 30630828). 30630828
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
BRAF V600K MAP2K1 P124L melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive VX-11e Preclinical Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). 25370473
BRAF V600K NRAS Q61K melanoma sensitive GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma sensitive VX-11e Preclinical - Cell culture Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF K601E Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). 22798288
BRAF K601E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Clinical Study Actionable In a clinical case study, a melanoma patient with BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). 28344857
BRAF K601E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase II Actionable In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). 23248257
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical Actionable In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 6 of the non-responding patients harbored BRAF K601E (PMID: 29320312; NCT02091141). 29320312
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601E (PMID: 26343582). 26343582
BRAF K601E melanoma no benefit Dabrafenib Phase I Actionable In a Phase I trial, no responses were demonstrated among three melanoma patients with non-V600 BRAF mutations, including two patients harboring BRAF K601E, following treatment with Tafinlar (dabrafenib), compared to a confirmed response rate of 50% in patients harboring BRAF V600 mutations (PMID: 22608338). 22608338
BRAF D594G NRAS G12D melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response PLX7904 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF D594G in culture (PMID: 28783719). 28783719
BRAF mutant IDH1 wild-type glioblastoma multiforme predicted - sensitive Nivolumab Clinical Study Actionable In a retrospective study, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab) compared to those did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). 30742119
BRAF mutant IDH1 wild-type glioblastoma multiforme predicted - sensitive Pembrolizumab Clinical Study Actionable In a retrospective study, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab) compared to those did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). 30742119
BRAF mut PTPN11 dec exp colorectal cancer sensitive PLX4720 Preclinical - Cell culture Actionable In a preclinical study, knocking down of Ptpn11 expression via shRNA sensitized BRAF mutant colorectal cancer cell lines to PLX4720 in culture (PMID: 26351322). 26351322
BRAF mut PTEN mut melanoma decreased response MEK1 Inhibitor E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 resulted in a cytostatic response in melanoma cell lines harboring both BRAF and PTEN mutations in culture and only inhibited tumor growth at very high doses in cell line xenograft models (PMID: 23039341). 23039341
BRAF mut PTEN mut melanoma predicted - sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 resulted in tumor regression in a melanoma cell line xenograft model co-harboring mutations in BRAF and PTEN (PMID: 28775144). 28775144
BRAF mut PTEN wild-type melanoma sensitive MEK1 Inhibitor E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 resulted in a cytocidal response in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture and inhibited tumor growth in cell line xenograft models (PMID: 23039341). 23039341
BRAF mut PTEN wild-type melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GSK2636771 + Binimetinib Preclinical Actionable In a preclinical study, GSK2636771 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + NVP-AEW541 Preclinical Actionable In a preclinical study, AZD6482 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit GSK2636771 + NVP-AEW541 Preclinical Actionable In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit GSK2636771 + LGX818 Preclinical Actionable In a preclinical study, GSK2636771 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + LGX818 Preclinical Actionable In a preclinical study, AZD6482 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib Preclinical Actionable In a preclinical study, AZD6482 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut STAG2 dec exp melanoma decreased response Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Zelboraf (vemurafenib) both in culture and in cell line xenograft models (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment in culture (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). 27500726
BRAF mut STAG2 dec exp melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Tafinlar (dabrafenib) in culture (PMID: 27500726). 27500726
BRAF mut + TP53 wild-type melanoma sensitive AMG 232 Preclinical - Cell line xenograft Actionable In a preclinical study, AMG 232 inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). 25567130
BRAF mut + TP53 wild-type melanoma sensitive CGM097 + LGX818 Preclinical Actionable In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). detail...
BRAF mut + TP53 wild-type colorectal cancer sensitive ABT-263 + CGM097 + Dabrafenib + PF-04217903 Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
BRAF mut NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). 26169970
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 Preclinical Actionable In a preclinical study, AZD6482 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib + LGX818 + BYL719 Preclinical Actionable In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 Preclinical Actionable In a preclincal study, AZD6482 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive NVP-AEW541 + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib Preclinical Actionable In a preclinical study, AZD6482 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit BYL719 + NVP-AEW541 Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BYL719 + GSK2636771 + LGX818 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of GSK2636771, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently inhibited tumor growth in xenograft models of a human melanoma cell line harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + NVP-AEW541 Preclinical Actionable In a preclinical study, AZD6482 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + LGX818 + BYL719 Preclinical Actionable In a preclinical study, combination treatment consisting of AZD6482, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GSK2636771 + Binimetinib Preclinical Actionable In a preclinical study, GSK2636771 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + LGX818 Preclinical Actionable In a preclinical study, GSK2636771 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + LGX818 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771, Encorafenib (LGX818), and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib + LGX818 + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Pictilisib Preclinical Actionable In a preclincal study, Pictilisib (GDC-0941) inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BYL719 + GSK2636771 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of GSK2636771 and Alpelisib (BYL719) synergized to inhibit proliferation of human melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture, and inhibited tumor growth in xenograft models of one cell line harboring these mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive TGX-221 Preclinical Actionable In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma decreased response Alpelisib Preclinical Actionable In a preclincal study, melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations were less sensitive to Alpelisib (BYL719)-induced growth inhibition in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit BYL719 + LGX818 Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and Encorafenib (LGX818) combination treatment did not enhance growth inhibition in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Encorafenib + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + NVP-AEW541 Preclinical Actionable In a preclinical study, GSK2636771 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive LGX818 + unspecified IGF-1R antibody Preclinical Actionable In a preclinical study, combination treatment consists of Encorafenib (LGX818) and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Alpelisib + Binimetinib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + BYL719 Preclinical Actionable In a preclinical study, AZD6482 and Alpelisib (BYL719) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut KRAS G12V melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, BRAF mutant melanoma cells over-expressing KRAS G12V were resistant to Selumetinib (AZD6244) and AZ628 combination treatment in culture (PMID: 26351322). 26351322
BRAF mutant colorectal cancer no benefit Regorafenib Phase II Actionable In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). 30120161
BRAF mutant colorectal cancer decreased response PLX4720 Preclinical - Cell culture Actionable In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). 26351322
BRAF mutant colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Phase Ib/II Actionable In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). detail... 28363909
BRAF mutant colon cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). 27655129
BRAF mutant melanoma sensitive Encorafenib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant colorectal cancer sensitive Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). 28611205
BRAF mutant thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase I Actionable In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). 23406027
BRAF mutant colorectal cancer sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant Advanced Solid Tumor predicted - sensitive MLN2480 Preclinical - Cell culture Actionable In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). detail...
BRAF mutant colorectal cancer sensitive HM95573 Preclinical - Cell line xenograft Actionable In a preclinical study, HM95573 inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant melanoma sensitive PET-16 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). 26984758
BRAF mutant Advanced Solid Tumor sensitive Obatoclax Preclinical Actionable In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). 22460902
BRAF mutant melanoma predicted - sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021). 29247021
BRAF mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). 27760111
BRAF mutant melanoma sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). 27307593
BRAF mutant non-small cell lung carcinoma predicted - sensitive Nivolumab Clinical Study Actionable In a clinical study, mutant BRAF correlated with prolonged duration on Opdivo (nivolumab) therapy compared to wild-type BRAF in non-small cell lung carcinoma patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant non-small cell lung carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). 28947956
BRAF mutant pancreatic adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant pancreatic cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive MEK1 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). 23039341
BRAF mutant colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). 28611205
BRAF mutant colorectal cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant stomach carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive Vemurafenib + Voruciclib Phase I Actionable In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). detail...
BRAF mutant Advanced Solid Tumor predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). detail...
BRAF mutant melanoma sensitive MLN2480 Phase I Actionable In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). detail...
BRAF mutant melanoma sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant colon cancer predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). 26140595
BRAF mutant colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). 26351322
BRAF mutant lung adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant Advanced Solid Tumor no benefit CC-90003 Phase I Actionable In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). detail...
BRAF mutant Advanced Solid Tumor sensitive Dabrafenib Phase I Actionable In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). 22608338
BRAF mutant Advanced Solid Tumor sensitive RAF709 Phase I Actionable In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). 29343524
BRAF mutant non-small cell lung carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). 28611198
BRAF mutant colorectal cancer predicted - resistant SYM004 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). 29423521
BRAF mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + BKM120 Preclinical - Cell culture Actionable In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). 27307593
BRAF mutant Advanced Solid Tumor decreased response XL147 Preclinical Actionable In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). 25637314
BRAF mutant melanoma predicted - sensitive ST-162 Preclinical - Cell line xenograft Actionable In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). 28775144
BRAF mutant melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). 25873592
BRAF mutant melanoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). 24422853
BRAF mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). 27488531
BRAF mutant colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mutant Advanced Solid Tumor predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). 26140595
BRAF mutant melanoma sensitive Tubastatin A Preclinical Actionable In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). 25957812
BRAF mutant colorectal cancer sensitive Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). 28363909
BRAF mutant Advanced Solid Tumor sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 demonstrated safety and preliminary efficacy, resulted in partial response in 14% (4/29), and prolonged stable disease in 48% (14/29) of advanced solid tumor patients harboring mutations in KRAS, NRAS, and/or BRAF (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF mutant cervix carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive S63845 + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). 27760111
BRAF mutant melanoma sensitive MEK1 Inhibitor E6201 + LY294002 Preclinical Actionable In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). 23039341
BRAF mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase II Actionable In a Phase II trial in patients with advanced melanoma, 5/6 patients exhibiting a response to selumetinib had BRAF-mutant tumors (PMID: 22048237). 22048237
BRAF mutant colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Panitumumab + Trametinib + Dabrafenib Phase Ib/II Actionable In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). 27770002
BRAF mutant colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase I Actionable In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). 28152546
BRAF mutant thyroid cancer sensitive HM95573 Preclinical - Cell culture Actionable In a preclinical study, HM95573 inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant multiple myeloma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mut TP53 mut colorectal cancer sensitive ABT-263 + Alpelisib + Dabrafenib + Erlotinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). 27659046
BRAF mut KRAS mut CDKN2A mut triple-receptor negative breast cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human triple negative breast cancer cells harboring mutant BRAF, KRAS, and CDKN2A were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
BRAF mut PTEN loss melanoma sensitive GSK2636771 + Pembrolizumab Preclinical Actionable In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor SAR260301 + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 and Selumetinib (AZD6244) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma sensitive SAR260301 Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma no benefit Pembrolizumab Preclinical Actionable In a preclinical study, Keytruda (pembrolizumab) resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma no benefit GSK2636771 Preclinical Actionable In a preclinical study, GSK2636771 resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma sensitive SAR260301 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut RB1 loss melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response Palbociclib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). 27488531
BRAF mut NRAS mut melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-847325 Preclinical - Cell culture Actionable In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). 25873592
BRAF mut NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). 26169970
BRAF mut KRAS mut melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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
APC Q1429fs BRAF N581S ERBB2 L755S rectum adenocarcinoma no benefit Fluorouracil + Leucovorin + Trastuzumab Clinical Study Actionable In a clinical case study, a rectal adenocarcinoma patient harboring APC Q1429fs, BRAF N581S, and ERBB2 L755S did not respond to Herceptin (trastuzumab) treatment in combination with Fluorouracil and Wellcovorin (leucovorin) (PMID: 27626067). 27626067
BRAF N581S Advanced Solid Tumor no benefit Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF N581S (PMID: 29320312; NCT02091141). 29320312
BRAF N581S lung 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 a lung adenocarcinoma patient harboring BRAF N581S in culture (PMID: 26140595). 26140595
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529M Advanced Solid Tumor predicted - sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF G469A non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) induced apoptosis and inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 25706985). 25706985
BRAF G469A lung adenocarcinoma sensitive PLX8394 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G469A in culture, and reduced tumor growth in xenograft models (PMID: 27834212). 27834212
BRAF G469A non-small cell lung carcinoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a non-small lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). 29903896
BRAF G469A non-small cell lung carcinoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a non-small cell lung cancer cell line harboring BRAF G469A demonstrated resistance to induction of apoptosis by Zelboraf (vemurafenib,) and treatment with Zelboraf (vemurafenib) was not effective in inhibiting growth in culture (PMID: 25706985). 25706985
BRAF G469A 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 BRAF G469A mutation in culture (PMID: 26090892). 26090892
BRAF G469A non-small cell lung carcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). 29903896
BRAF G469A non-small cell lung carcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture, and prevented Mekinist (trametinib)-related activation of AKT and resulted in increased induction of apoptosis compared to either agent alone (PMID: 25706985). 25706985
BRAF G469A non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased viability and enhanced ERK inhibition compared to either agent alone, in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 28947956). 28947956
BRAF G469A head and neck cancer sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021). 29247021
BRAF G469A Advanced Solid Tumor resistant Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G469A (PMID: 29320312; NCT02091141). 29320312
BRAF G469A Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469A (PMID: 26343582). 26343582
BRAF G469A small intestine carcinoma sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021). 29247021
BRAF G469A non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). 29903896
BRAF G469A lung cancer resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of lung cancer cells harboring BRAF G469A in culture (PMID: 30104724). 30104724
BRAF K601T Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601T (PMID: 26343582). 26343582
BRAF G469L lung adenocarcinoma no benefit Vemurafenib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring BRAF G469L did not respond to Zelboraf (vemurafenib) therapy (PMID: 24035431). 24035431
BRAF K601N hematologic cancer sensitive LY3009120 LY3009120 Preclinical - Cell culture Actionable In a preclinical study, a hematological tumor cell line harboring BRAF K601N demonstrated sensitivity to LY3009120 in culture (PMID: 26732095). 22798288
BRAF K601N Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601N (PMID: 26343582). 26343582
BRAF act mut non-small cell lung carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). 29343524
BRAF act mut thyroid cancer sensitive Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). 23489023
BRAF act mut colorectal cancer no benefit Venetoclax + VX-11e Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
BRAF act mut melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF act mut Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). detail...
BRAF act mut colorectal cancer predicted - sensitive VX-11e + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
BRAF act mut Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). 24422853
BRAF act mut melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). 22084396
BRAF V600E MAP2K1 I111N melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 I111N melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). 28655712
MAP2K1 Q56P BRAF V600E melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the MEK inhibitor selumetinib (AZD6244) cell culture. 19915144
MAP2K1 Q56P BRAF V600E melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the B-RAF inhibitor PLX4720 in culture (PMID: 19915144). 19915144
MAP2K1 Q56P BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, combined treatment with selumetinib and PLX4720 strongly suppressed the emergence of resistant MAP2K1 mutations in BRAF V600E cells in culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma conflicting Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E MAP2K1 P387S NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). 22389471
BRAF V600E colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colon cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). 16273091
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Ganetespib + TAK-733 Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E melanoma sensitive EBI-907 Preclinical - Cell line xenograft Actionable In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). 26810733
BRAF V600E colorectal cancer sensitive Cetuximab + Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E pilocytic astrocytoma sensitive Dabrafenib Clinical Study Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in a near complete response and resolution of leptomeningeal dissemination in a patient with pilocytic astrocytoma harboring BRAF V600E (PMID: 28784858). 28784858
BRAF V600E non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive BI 882370 + Afatinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Gilotrif (afatinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). 26916115
BRAF V600E colorectal cancer sensitive Cetuximab + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 22281684). 22281684
BRAF V600E colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colon carcinoma sensitive RXDX-105 Preclinical - Cell line xenograft Actionable In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human colon carcinoma cell line (PMID: 22319199). 22319199
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI 882370 + Trametinib Preclinical Actionable In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). 26916115
BRAF V600E melanoma sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in melanoma cell lines harboring BRAF V600E in culture (PMID: 26208524). 26208524
BRAF V600E melanoma sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 of 2 melanoma patients harboring BRAF V600E, who remained on treatment for over 249 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF V600E colorectal adenocarcinoma sensitive DEL-22379 Preclinical - Pdx Actionable In a preclinical study, DEL-22379 inhibited tumor growth in a colorectal adenocarcinoma patient-derived xenograft model harboring BRAF V600E (PMID: 26267534). 26267534
BRAF V600E thyroid cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive RAF709 Preclinical - Cell culture Actionable In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 29343524). 29343524
BRAF V600E glioblastoma multiforme sensitive BI2536 + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). 26573800
BRAF V600E melanoma sensitive CCT196969 Preclinical - Pdx Actionable In a preclinical study, CCT196969 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). 25500121
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011
BRAF V600E melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF V600E melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive DETD-35 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, DETD-35 and Zelboraf (vemurafenib) synergistically inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). 27048951
BRAF V600E skin melanoma sensitive Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor Ganetespib destabilized BRAF, especially BRAF V600E, resulted in loss of cell viability in culture and antitumor effects in cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI 882370 + Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Mekinist (trametinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). 26916115
BRAF V600E colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Cetuximab + Encorafenib Phase III Actionable In a Phase III (BEACON CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment resulted in an objective response rate of 48% (14/29, 3 complete responses), and stable disease in 52% (15/29) of patients with BRAF V600E metastatic colorectal cancer, with a median progression-free survival of 8.0 months (Annals of Oncology, Volume 29, Issue suppl_5; NCT02928224). detail...
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib FDA approved Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, which included patients identified to harbor BRAF V600E or BRAF V600K (PMID: 27480103; NCT01689519). 27480103
BRAF V600E colorectal cancer sensitive Ulixertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in colorectal cancer cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). 28939558
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, PLX4720 and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PAC-1 + Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of PAC-1 to Mekinist (trametinib) and Zelboraf (vemurafenib) led to greater levels of caspase-3 activity and apoptosis in melanoma cells harboring BRAF V600E when compared to Zelboraf (vemurafenib) and Mekinist (trametinib) treatment without PAC-1 (PMID: 27297867). 27297867
BRAF V600E melanoma sensitive Gefitinib + PLX4720 Preclinical Actionable In a preclinical study, Iressa (gefitinib) in combination with PLX4720 inhibited proliferation and tumorigenicity in human melanoma cell line harboring BRAF V600E and resistant to Braf inhibition in culture and in animal models (PMID: 23242808). 23242808
BRAF V600E thyroid cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E melanoma sensitive Dabrafenib FDA approved Actionable In a Phase III clinical trial (BREAK-3) that supported FDA approval, Tafinlar (dabrafenib) improved median progression-free survival compared to Deticene (dacarbazine) (5.1 vs 2.7 months, HR=0.3, p<0.0001) in patients with BRAF V600E positive melanoma (PMID: 22735384; NCT01227889). 22735384
BRAF V600E glioblastoma multiforme decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). 26573800
BRAF V600E renal cell carcinoma sensitive Vemurafenib Clinical Study Actionable In a clinical case study, a patient with metastatic renal cell carcinoma harboring BRAF V600E demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26918217). 26918217
BRAF V600E non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634). 27283860 27080216 detail... 28919011
BRAF V600E non-small cell lung carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Guideline Actionable Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations (NCCN.org). detail...
BRAF V600E melanoma sensitive PLX4720 + Navitoclax Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and navitoclax (ABT-263) worked synergistically to inhibit growth and increase apoptosis of BRAF V600E mutant melanoma cells in culture and in xenografts (PMID: 24983357). 24983357
BRAF V600E melanoma sensitive DETD-35 Preclinical - Cell line xenograft Actionable In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). 27048951
BRAF V600E melanoma sensitive SCH772984 Preclinical Actionable In a preclinical study, SCH772984 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab) is not indicated for use in rectum cancer patients with BRAF V600E unless it is given with a BRAF inhibitor (NCCN.org). detail...
BRAF V600E pleomorphic xanthoastrocytoma predicted - sensitive Vemurafenib Phase II Actionable In a Phase II clinical trial (VE-BASKET), Zelboraf (vemurafenib) treatment of BRAF V600E mutant pleomorphic xanthoastrocytomas resulted in a 42.9% (3/7) objective response rate, a 5.7-month median progression-free survival, and best overall response rates of 14.3% (1/7) for complete response, 28.6% (2/7) for partial response, and 42.9% (3/7) for stable disease (PMID: 30351999; NCT01524978). 30351999
BRAF V600E colorectal cancer sensitive Panitumumab + Dabrafenib Phase Ib/II Actionable In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). detail...
BRAF V600E colorectal cancer sensitive Panitumumab + Dabrafenib Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E melanoma sensitive Vemurafenib + SBI-060756 Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) in combination with SBI-0640756 inhibited the association of eIF4G1 and eIF4E in Zelboraf (vemurafenib) resistant human melanoma cell lines harboring BRAF V600E in culture and reduced tumor growth in xenograft models (PMID: 26603897). 26603897
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive SCH772984 Preclinical Actionable In a preclinical study, SCH772984 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E glioblastoma multiforme predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in stable disease lasted for more than 16 months in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 29632053). 29632053
BRAF V600E thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E colorectal cancer sensitive BI 882370 + Cetuximab Preclinical Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). 26916115
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E colon cancer predicted - sensitive Cetuxmab + Sorafenib Clinical Study Actionable In a clinical case report, a patient with metastatic colon cancer harboring BRAF V600E demonstrated a mixed radiographic response, with slight progression in some locations, however, response or stable disease for 7 months in other locations following treatment with the combination of Nexavar (sorafenib) and Erbitux (cetuximab) (PMID: 23792568). 23792568
BRAF V600E melanoma decreased response Nivolumab Clinical Study Actionable In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). 30630828
BRAF V600E melanoma sensitive Imatinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gleevec (imatinib) and PLX4720 enhanced antitumor efficacy of melanoma cells harboring BRAF V600E, demonstrating decreased cell survival in xenograft models, and decreased phosphorylation of Mapk1 in culture (PMID: 27924459). 27924459
BRAF V600E colorectal cancer sensitive PLX4720 + TAK-632 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and TAK-632 combination treatment resulted in durable inhibition of Erk signaling and tumor growth in xenograft models of colorectal cancer cells harboring BRAF V600E (PMID: 27523909). 27523909
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma no benefit SHP099 Preclinical Actionable In a preclinical study, SHP099 did not inhibit proliferation or ERK activation in a melanoma cell line harboring BRAF V600E in culture (PMID: 27362227). 27362227
BRAF V600E neuroendocrine tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). 27048246
BRAF V600E colorectal cancer sensitive BGB-283 + Cetuximab Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 26208524). 26208524
BRAF V600E colorectal cancer sensitive Dabrafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation had increased sensitivity to Tafinlar (dabrafenib) in culture compared to cell lines with wild-type BRAF (PMID: 24885690). 24885690
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Refametinib Preclinical Actionable In a preclinical study, Refametinib (BAY86-9766) inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). 19706763
BRAF V600E melanoma sensitive PLX4720 + Tivozanib Preclinical Actionable In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E colorectal cancer sensitive Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E malignant glioma predicted - sensitive Vemurafenib Phase II Actionable In a Phase II clinical trial (VE-BASKET), treatment of patients with gliomas harboring BRAF V600E mutations with Zelboraf (vemurafenib) resulted in a 25% (6/24) objective response rate, 5.5-month median progression free survival, 28.2 month median overall survival, and best overall response rates of 4.2% (1/24) for complete response, 20.8% (5/24) for partial response, and 41.7% (10/24) for stable disease (PMID: 30351999; NCT01524978). 30351999
BRAF V600E rectum cancer sensitive Vemurafenib + Panitumumab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Vectibix (panitumumab), and Irinotecan combination therapy is included in guidelines for advanced or metastatic rectum cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical Actionable In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E melanoma predicted - sensitive RAF265 Phase I Actionable In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). 28719152
BRAF V600E colon neuroendocrine neoplasm predicted - sensitive Dabrafenib Clinical Study Actionable In a clinical case study, Tafinlar (dabrafinib) treatment of a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation resulted in stable disease for 6 months before disease progression (PMID: 30181415). 30181415
BRAF V600E pleomorphic xanthoastrocytoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in clinical benefit lasted for 16 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). 29632053
BRAF V600E melanoma sensitive INU-152 Preclinical - Cell line xenograft Actionable In a preclinical study, INU-152 reduced MEK and ERK phosphorylation and growth of a melanona cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 28645859). 28645859
BRAF V600E Advanced Solid Tumor sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited Erk phosphorylation and cell proliferation in BRAF V600E expressing cells in culture (PMID: 20538618). 20538618
BRAF V600E hairy cell leukemia not applicable N/A Guideline Diagnostic BRAF V600E is diagnostic and aids distinguishing classic hairy cell leukemia (HCL-C) from variant hairy cell leukemia (HCL-V) and other B-cell lymphomas and leukemias (PMID: 29118233). 29118233
BRAF V600E colorectal cancer sensitive BGB-283 Preclinical - Pdx & cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in colorectal cancer cell lines harboring BRAF V600E in culture, and resulted in partial tumor regression in both cell line and patient-derived xenograft models (PMID: 26208524). 26208524
BRAF V600E melanoma sensitive DEL-22379 Preclinical - Cell line xenograft Actionable In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). 26267534
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive Alpelisib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alpelisib (BYL719) and PLX4720 enhanced antitumor activity in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Akt signaling in culture (PMID: 27924459). 27924459
BRAF V600E colorectal cancer sensitive Lapatinib + Panobinostat Preclinical Actionable In a preclinical study, Tykerb (lapatinib) and Faridak (panobinostat) worked synergistically to inhibit growth of BRAF V600E mutant colorectal cancer cells in culture (PMID: 21464044). 21464044
BRAF V600E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E melanoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). 27488531
BRAF V600E melanoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 + Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in significant tumor regression in melanoma cell line xenograft models harboring BRAF V600E and demonstrated a 56% (5/9) complete response rate (PMID: 27488531). 27488531
BRAF V600E colorectal cancer sensitive Vemurafenib + Panitumumab Phase I Actionable In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 25589621). 25589621
BRAF V600E melanoma sensitive Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E larynx cancer predicted - sensitive Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with larynx cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). 29320312
BRAF V600E melanoma sensitive PAC-1 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PAC-1 and Zelboraf (vemurafenib) resulted in a synergistic effect when treating melanoma cells harboring BRAF V600E in culture and xenograft models, demonstrating increased apoptosis and decreased tumor volume (PMID: 27297867). 27297867
BRAF V600E thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case report, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). 27697975
BRAF V600E thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 69% (11/16; 1 complete response and 10 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29072975; NCT02034110). 29072975
BRAF V600E colon cancer sensitive GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). 19276360
BRAF V600E colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E glioblastoma multiforme sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E colorectal cancer sensitive PLX7904 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX7904 inhibited survival of colorectal cancer cells harboring BRAF V600E in culture and demonstrated anti-tumor activity in cell line xenograft models (PMID: 26466569). 26466569
BRAF V600E melanoma sensitive Erlotinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Tarceva (erlotinib) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models and culture (PMID: 27924459). 27924459
BRAF V600E hairy cell leukemia sensitive Vemurafenib Phase II Actionable In two Phase II clinical studies, patients with refractory hairy cell leukemia harboring BRAF V600E responded to Zelboraf (vemurafenib) with overall response rates of 96% (25/26) and 100% (24/24) as well as complete response rates of 35% (9/26) and 42% (10/24) with median follow up times of 8 and 12 weeks, respectively (PMID: 26352686). 26352686
BRAF V600E colon cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Navitoclax Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E rectum cancer sensitive Vemurafenib + Cetuximab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Erbitux (cetuximab), and Camptosar (irinotecan) combination therapy is included in guidelines for advanced or metastatic rectum cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E melanoma sensitive Encorafenib Preclinical - Cell line xenograft Actionable In preclinical studies, Encorafenib (LGX818) treatment of human melanoma xenograft models with BRAF V600E significantly decreased Mek activation and resulted in tumor regression (Cancer Res: 72(8) Suppl 1, Abstract #3790). detail...
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase II Actionable In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). 22048237
BRAF V600E melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited survival of melanoma cell lines harboring monomeric BRAF V600E as well as cells harboring the Zelboraf (vemurafenib)-resistant dimeric BRAF V600E in culture (PMID: 26466569). 26466569
BRAF V600E thyroid cancer sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive Saracatinib Preclinical Actionable In a preclinical study, saracatinib inhibited proliferation of human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). 23242808
BRAF V600E salivary gland carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Case Reports/Case Series Actionable In a clinical case report, combined Tafinlar (dabrafenib) and Mekinist (trametinib) treatment of a patient with salivary duct carcinoma harboring BRAF V600E resulted in a reduction of metastatic lesions and stable disease lasting 13 months followed by disease progression (PMID: 30323086). 30323086
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib Phase II Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 43% (6/14, 1 complete response, 5 partial response) in patients with non-small cell lung cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 2 patients (PMID: 29320312; NCT02091141). 29320312
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib Clinical Study Actionable In a clinical case study, a non-small cell lung cancer patient harboring a BRAF V600E mutation had a complete response after treatment with Zelboraf (vemurafenib) (PMID: 23733758). 23733758
BRAF V600E melanoma sensitive MEK1 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell lines harboring BRAF V600E mutation in culture (PMID: 24448821). 24448821
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RO4987655 Preclinical - Cell culture Actionable In a preclinical study, RO4987655 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). 26438159
BRAF V600E melanoma sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Refametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Refametinib (BAY86-9766) inhibited growth of melanoma cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). 19706763
BRAF V600E malignant glioma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). 27217440
BRAF V600E colorectal cancer resistant SHP099 Preclinical - Cell culture Actionable In a preclincial study, colorectal cancer cell lines harboring BRAF V600E demonstrated resistance to SHP099 in culture (PMID: 27362227). 27362227
BRAF V600E colon adenocarcinoma not applicable N/A Phase III Emerging In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). 26768652
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E colorectal cancer sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 25500121, PMID: 15294323). 25500121 15294323
BRAF V600E lung cancer sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients with lung cancer each harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E melanoma sensitive Cediranib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and Cediranib (AZD-2171) worked synergistically to inhibit cell growth and induce apoptosis in PLX4720-resistant human melanoma cell lines harboring BRAF V600E in culture and to suppress tumor growth in xenograft models (PMID: 26461489). 26461489
BRAF V600E melanoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited cell invasion, cell signaling, and proliferation in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture and in animal models (PMID: 23242808). 23242808
BRAF V600E melanoma sensitive S3I-201 Preclinical Actionable In a preclinical study, S3I-201 inhibited cell invasion and Stat3 signaling in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). 23242808
BRAF V600E colon cancer sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E melanoma sensitive Encorafenib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928). 28351928
BRAF V600E melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + SCH772984 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable inhibition of Erk signaling and proliferation of melanoma cells overexpressing BRAF V600E in culture (PMID: 28714990). 28714990
BRAF V600E colorectal cancer sensitive CCT196969 Preclinical - Cell culture Actionable In a preclinical study, CCT196969 inhibited growth of BRAF-mutant colorectal cancer cell lines in culture (PMID: 25500121), which have been reported to harbor BRAF V600E (PMID: 15294323). 25500121 15294323
BRAF V600E non-small cell lung carcinoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E non-small cell lung carcinoma sensitive Dabrafenib Phase II Actionable In a Phase II trial, 33% (26/78) of previously treated non-small cell lung carcinoma patients harboring BRAF V600E demonstrated an overall response, which included all partial responses, when treated with Tafinlar (dabrafenib) while 67% (4/6) receiving Tafinlar (dabrafenib) as a first-line treatment achieved partial responses (PMID: 27080216; NCT01336634). 27080216
BRAF V600E thyroid cancer conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, thyroid cancer cells harboring BRAF V600E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF V600E thyroid cancer conflicting Vemurafenib Clinical Study Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). 29320312
BRAF V600E melanoma sensitive Vemurafenib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E glioblastoma multiforme sensitive BI2536 Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). 26573800
BRAF V600E colon cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited Braf V600E in vitro and inhibited growth of human colon cancer cells harboring BRAF V600E in culture (PMID: 21325073, PMID: 24042735). 24042735 21325073
BRAF V600E Advanced Solid Tumor sensitive PLX4720 Preclinical Actionable In a preclinical study, PLX4720 inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dasatinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma resistant RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 30104724). 30104724
BRAF V600E Advanced Solid Tumor predicted - sensitive PF3644022 + PF-477736 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of transformed cells over expressing BRAF V600E in culture, while single agent inhibition had no effect (PMID: 26140595). 26140595
BRAF V600E colorectal cancer sensitive EBI-907 Preclinical - Cell line xenograft Actionable In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of colorectal cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). 26810733
BRAF V600E colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 demonstrated modest efficacy in patient-derived xenograft models of colorectal cancer harboring BRAF V600E, resulted in tumor growth inhibition or regression, but relapse upon discontinuation of treatment (PMID: 28611205). 28611205
BRAF V600E melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E melanoma sensitive Vemurafenib FDA approved Actionable In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848; NCT01006980). 28961848 21639808
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase II Actionable In a Phase II trial, 20% (8/41) of melanoma patients with BRAF V600 mutations had a partial response to Binimetinib (MEK162) (PMID: 23414587). 23414587
BRAF V600E thyroid cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dasatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Selumetinib (AZD6244) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive ASN003 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma xenograft model harboring BRAF V600E demonstrated tumor regression when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). detail...
BRAF V600E melanoma sensitive BI-69A11 Preclinical Actionable In a preclinical study, BI-69A11 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma sensitive Ulixertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in melanoma cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). 28939558
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). 24885690
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib FDA approved Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). 25399551
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Phase II Actionable In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). 28268064
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600E, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600E colon cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colon neuroendocrine neoplasm no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Clinical Study Actionable In Phase II trial, Mektovi (binimetinib) therapy in a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation who had previously progressed on Tafinlar (dabrafinib) resulted in disease progression after two cycles (PMID: 30181415; NCT01885195). 30181415
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Phase I Actionable In a Phase I trial, Cotellic (cobimetinib) treatment resulted in a confirmed partial response in six melanoma patients harboring BRAF V600E (PMID: 27424159). 27424159
BRAF V600E colorectal cancer sensitive Vemurafenib + Gefitinib Preclinical Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Iressa (gefitinib) decreased the number of viable colorectal cancer cells harboring a BRAF V600E mutation in cell culture (PMID: 22448344). 22448344
BRAF V600E colorectal cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Panitumumab + Trametinib Phase I Actionable In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E Advanced Solid Tumor sensitive SB590885 Preclinical Actionable In a preclinical study, SB590885 inhibited inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RO5126766 Preclinical - Cell culture Actionable In a preclinical study, RO5126766 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). 26438159
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) inhibited tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 28649441). 28649441
BRAF V600E melanoma sensitive LY3009120 LY3009120 Preclinical Actionable In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). 26343583
BRAF V600E non-small cell lung carcinoma sensitive Vemurafenib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab) is not indicated for use in rectum cancer patients with BRAF V600E unless it is given with a BRAF inhibitor (NCCN.org). detail...
BRAF V600E melanoma sensitive CCT241161 Preclinical - Pdx Actionable In a preclinical study, CCT241161 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). 25500121
BRAF V600E colorectal cancer sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) showed activity in patients with advanced metastatic colorectal cancer harboring a BRAF V600E mutation, resulting in a median progression-free survival of 4 months and a best response of stable disease in 66.7% (12/18) (Ann Oncol (2014) 25 (suppl 4): iv182-iv183). detail...
BRAF V600E melanoma sensitive PLX4720 + Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). 27924459
BRAF V600E melanoma sensitive GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of melanoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models of BRAF V600E-positive melanoma, including models with BRAF-inhibitor resistance (PMID: 25873592). 25873592
BRAF V600E neuroendocrine tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Vemurafenib Clinical Study Actionable In a clinical case study, Mekinist (trametinib) and Zelboraf (vemurafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). 27048246
BRAF V600E colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Panitumumab + Trametinib + Dabrafenib Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E melanoma sensitive SBI-0640726 Preclinical Actionable In a preclinical study, SBI-0640726 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma decreased response Pembrolizumab Clinical Study Actionable In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). 30630828
BRAF V600E colorectal cancer sensitive Vemurafenib + Erlotinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Tarceva (erlotinib) resulted in improved inhibition of tumor growth in BRAF V600E mutant human colon cancer cell line xenograft models compared to either drug as monotherapy (PMID: 22448344). 22448344
BRAF V600E lung carcinoma resistant Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) failed to induce apoptosis in lung carcinoma cells expressing BRAF V600E (PMID: 22649091). 22649091
BRAF V600E ganglioglioma predicted - sensitive Dabrafenib Clinical Study Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in partial response 8 weeks after therapy initiation in a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E, but disease progression occurred at 40 weeks due to acquired resistance (PMID: 29880583). 29880583
BRAF V600E colorectal cancer sensitive Vemurafenib + Cetuximab Clinical Study Actionable In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer (PMID: 24523613). 24523613
BRAF V600E colorectal cancer sensitive Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E Advanced Solid Tumor sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited viability of a variety of cancer cell lines harboring BRAF V600E in culture (PMID: 26208524). 26208524
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). 25309914
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) decreased tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 23942066). 23942066
BRAF V600E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cediranib + Selumetinib + PLX4720 Preclinical Actionable In a preclinical study, PLX4720, Cediranib (AZD-2171) and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E malignant glioma predicted - sensitive Everolimus + PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). 27217440
BRAF V600E colon cancer sensitive Vemurafenib + Panitumumab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Vectibix (panitumumab), and Irinotecan combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E thyroid cancer sensitive CLM3 Preclinical Actionable In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression in thyroid cancer cells harboring BRAF V600E in culture (PMID: 24423321). 24423321
BRAF V600E Advanced Solid Tumor sensitive Vemurafenib Phase II Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 46% (12/26, 2 complete response, 10 partial response) in patients with advanced solid tumors harboring BRAF V600E, but only 4% (1/23, 1 partial response) in patients harboring non-V600 BRAF mutations (PMID: 29320312; NCT02091141). 29320312
BRAF V600E colorectal cancer sensitive LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 inhibited survival of melanoma cell lines harboring BRAF V600E in cell culture, cell line xenograft and patient-derived xenograft (PDX) models (PMID: 19276360). 19276360
BRAF V600E Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). 24422853
BRAF V600E melanoma no benefit Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Ibrance (palbociclib) in a melanoma cell line xenograft model harboring BRAF V600E resulted in no benefit, demonstrating low but continuous growth (PMID: 27488531). 27488531
BRAF V600E colorectal cancer sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). 27523909
BRAF V600E ovarian cancer predicted - sensitive Vemurafenib Phase II Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 50% (2/4, 2 partial response) in patients with ovarian cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 1 patient (PMID: 29320312; NCT02091141). 29320312
BRAF V600E non-small cell lung carcinoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E melanoma sensitive RXDX-105 Preclinical - Cell line xenograft Actionable In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human melanoma cell line (PMID: 22319199). 22319199
BRAF V600E colorectal cancer sensitive DT01 + Fluorouracil + Oxaliplatin Preclinical - Cell line xenograft Actionable In a preclinical study, DT01 increased sensitivity of human colorectal cancer (CRC) cells harboring BRAF V600E to Eloxatin (oxaliplatin) and Adrucil (5-fluorouracil), and the combination resulted in decreased liver tumor growth in CRC cell line xenograft metastasis models (PMID: 26637369). 26637369
BRAF V600E glioblastoma multiforme decreased response PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). 26573800
BRAF V600E thyroid cancer sensitive BGB-283 Phase I Actionable In a Phase I trial, BGB-283 resulted in partial response in 1 thyroid cancer patient harboring BRAF V600E, who remained on treatment for over 481 days (AACR Annual Meeting, Apr 2016, abstract # CT005). detail...
BRAF V600E melanoma sensitive SB590885 Preclinical - Cell culture Actionable In a preclinical study, SB590885 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E thyroid cancer sensitive Lapatinib + Vemurafenib Preclinical Actionable In a preclinical study, the combination of Tykerb (lapatinib) and Zelboraf (vemurafenib) inhibited growth of thyroid cancer cells harboring a BRAF V600E mutation in culture and in BRAF-mutant mouse models of thyroid cancer (PMID: 23365119). 23365119
BRAF V600E malignant glioma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Everolimus + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and Afinitor (everolimus) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). 27217440
BRAF V600E colorectal cancer sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). 21170960
BRAF V600E melanoma sensitive SBI-755199 Preclinical Actionable In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). 26603897
BRAF V600E melanoma sensitive PLX4720 + Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Adriamycin (doxorubicin) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and inhibition of cell growth in culture (PMID: 27924459). 27924459
BRAF V600E melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E colon cancer sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colon cancer sensitive Vemurafenib + Cetuximab + Irinotecan Guideline Actionable Zelboraf (vemurafenib), Erbitux (cetuximab), and Camptosar (irinotecan) combination therapy is included in guidelines for advanced or metastatic colon cancer patients harboring BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive INU-152 Preclinical - Cell line xenograft Actionable In a preclinical study, INU-152 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture, and reduced tumor growth in BRAF V600E-mutant colorectal cancer cell line xenograft models (PMID: 28645859). 28645859
BRAF V600E colorectal cancer no benefit Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). 22281684
BRAF V600E colorectal cancer no benefit Vemurafenib Phase II Actionable In a Phase II trial, Zelboraf (vemurafenib) did not demonstrate meaningful clinical activity as a single agent, resulted in partial response in 5% (1/21) and stable disease in 33% (7/21) of patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 26460303; NCT00405587). 26460303
BRAF V600E colorectal cancer no benefit Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cell lines harboring BRAF V600E demonstrated decreased response to Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical - Cell line xenograft Actionable In a preclinical study, CI-1040 inhibited growth of a human ovarian cancer cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). 19018267
BRAF V600E papillary thyroid carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RO5126766 Preclinical Actionable In a preclinical study, RO5126766 inhibited Mek signaling and increased radioiodide uptake and response in transgenic animal models of papillary thyroid carcinoma driven by BRAF V600E (PMID: 27669459). 27669459
BRAF V600E TP53 Q192K colon cancer sensitive Vemurafenib + Panitumumab Clinical Study Actionable In a clinical study, a colon cancer patient harboring BRAF V600E and TP53 Q192K demonstrated a partial response when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 28514312). 28514312
BRAF V600E MAP2K1 K57E melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, expression of MAP2K1 K57E in a melanoma cell line harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600E KRAS mutant colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical Actionable In a preclinical study, over expression of BRAF V600E in KRAS-mutant colorectal cancer cells resulted in resistance to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E KRAS mutant colorectal cancer sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of KRAS-mutant melanoma cells over expressing BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E PTEN loss TP53 wild-type colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor MLN0128 + PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, Sapanisertib (MLN0128) and PD-0325901 synergistically inhibited Erk and PI3K signaling and proliferation, induced apoptosis in TP53-wild-type colorectal cancer cells harboring BRAF V600E and PTEN loss in culture and in cell line xenograft models (PMID: 26272063). 26272063
BRAF V600E MAP2K1 V211D melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by CI-1040 in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (Ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 V211D colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Selumetinib (AZD6244) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired secondary resistant mutation of MAP2K1 V211D (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 V211D melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by Selumetinib (AZD6244) in cell culture (PMID: 19915144). 19915144
BRAF V600E MAP2K1 V211D colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in cell culture (PMID: 25370473). 25370473
BRAF V600E MAP2K1 G128V melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 G128V melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 P124L melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 P124L melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E KRAS amp colorectal cancer resistant SCH772984 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS amplification and subsequent resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS amp colorectal cancer resistant Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Tafinlar (dabrafenib) combination treatment in culture, likely due to the acquired KRAS amplification (PMID: 27312529). 27312529
BRAF V600E 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 G12D colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture, likely due to the acquisition of KRAS G12D (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS G12D colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a KRAS G12D mutation and subsequent resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture (PMID: 27312529). 27312529
BRAF V600E CSF1R positive melanoma sensitive Pexidartinib + Vemurafenib Preclinical Actionable In a preclinical study, a melanoma mouse model harboring BRAF V600E treated with Zelboraf (vemurafenib) demonstrated a greater drug induced sensitivity when treatment was combined with PLX3397, resulting in increased infiltration of lymphocytes via Csf1r inhibition and elevated antitumor activity (PMID: 25939769). 25939769
BRAF V600E PTEN loss melanoma sensitive Pictilisib + PLX4720 Preclinical Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and PTEN loss demonstrated sensitivity when treated with a combination of Pictilisib (GDC-0941) and PLX4720, resulting in decreased cell proliferation in culture (PMID: 24265153). 24265153
BRAF V600E PTEN loss melanoma resistant Everolimus Clinical Study Actionable In a clinical study, a melanoma patient harboring PTEN loss and BRAF V600E demonstrated resistance to Afinitor (everolimus) treatment, resulting in progressive disease (PMID: 20664172). 20664174 20664172
BRAF V600E PTEN loss melanoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600E (PMID: 25637314). 25637314
BRAF V600E PTEN loss melanoma sensitive GDC0879 + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, GDC0879 and Pictilisib (GDC-0941) synergistically inhibited survival of melanoma cell lines harboring BFAF V600E and PTEN loss in cell culture (PMID: 19276360). 19276360
BRAF V600E PTEN loss melanoma sensitive GSK2636771 + unspecified PD-1 antibody Preclinical Actionable In a preclinical study, treatment with the combination of GSK2636771 and a PD-1 antibody resulted in greater tumor infiltration of T-cells and tumor growth inhibition in mouse melanoma models expressing BRAF V600E with PTEN loss compared to either agent alone (PMID: 26645196). 26645196
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E BRAF T529I Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E NRAS G12V melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). 26267534
BRAF V600E NRAS G12V melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). 26267534
BRAF V600E ERBB2 over exp KRAS A146V stomach cancer predicted - resistant Trastuzumab Clinical Study Actionable In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified KRAS A146V and BRAF V600E in 1 patient demonstrating primary resistance to Herceptin (trastuzumab) (PMID: 29208673). 29208673
BRAF V600E MAP2K1 H119P melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E treated with Selumetinib (AZD6244) in culture demonstrated resistance, which was a result of the resistance mutation, MAP2K1 H119P (PMID: 19915144). 19915144
BRAF V600E MAP2K1 C121S melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 C121S melanoma sensitive MEK1 Inhibitor E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma resistant PLX4720 Preclinical Actionable In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). 24265154
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Zelboraf (vemurafenib)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 C121S melanoma decreased response Vemurafenib Clinical Study Actionable In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). 21383288
BRAF V600E MAP2K1 C121S melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E MAP2K1 C121S melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). 24448821
BRAF V600E MAP2K1 K57T refractory hairy cell leukemia predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Vemurafenib + Cobimetinib Clinical Study Actionable In a clinical case study, a single patient with hairy cell leukemia who relapsed after initial response to Zelboraf (vemurafenib) was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant, and demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). 30341394
BRAF V600E MAP2K1 K57T hairy cell leukemia predicted - resistant Vemurafenib Clinical Study Actionable In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). 30341394
BRAF V600E NRAS Q61K melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K melanoma sensitive XL888 Preclinical Actionable In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). 22351686
BRAF V600E NRAS Q61K melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). 21107323
BRAF V600E NRAS Q61K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). 22389471
BRAF V600E NRAS Q61K lung adenocarcinoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Clinical Study Actionable In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). 29631033
BRAF V600E NRAS Q61K NRAS A146T melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 I103N melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical Actionable In a preclinical study, over expression of MAPK21 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 I103N melanoma sensitive DEL-22379 Preclinical - Cell culture Actionable In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). 26267534
BRAF V600E MAP2K1 V60E melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). 24265153
BRAF V600E MAP2K1 V60E melanoma sensitive VRT11E Preclinical Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). 24265153
BRAF V600E KRAS A146T colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Erbitux (cetuximab) and Encorafenib (LGX818) combination treatment in culture, likely due to the acquired secondary resistance mutation KRAS A146T (PMID: 27312529). 27312529
BRAF V600E KRAS A146T colorectal cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor 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 + 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 MAP2K1 Q56P melanoma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 Q56P melanoma sensitive Ulixertinib Preclinical - Cell culture Actionable In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). 28655712
BRAF V600E MAP2K1 Q56P melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + Dabrafenib Preclinical Actionable In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). 22389471
BRAF V600E MAP2K1 Q56P melanoma resistant Dabrafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). 22389471
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Vemurafenib + Cetuximab Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant LGX818 + Cetuximab + BYL719 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to combination treatment consisting of Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) in culture, likely due to the acquisition of KRAS A146V and A146T secondary resistance mutations (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired KRAS A146V and A146T mutations and subsequent resistance to Erbitux (cetuximab), Encorafenib (LGX818), and Alpelisib (BYL719) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Selumetinib (AZD6244) in culture (PMID: 27312529). 27312529
BRAF V600E KRAS A146T KRAS A146V colorectal cancer resistant Cetuximab + 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 NRAS A146T MAP2K1 P387S melanoma resistant Vemurafenib Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response GSK2126458 Preclinical Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma no benefit Dabrafenib + GSK2126458 Preclinical Actionable In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). 22389471
BRAF V600E NRAS A146T MAP2K1 P387S melanoma decreased response