Molecular Profile Detail

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF L485Y lung non-small cell carcinoma resistant BRAF Inhibitor 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 F247L Advanced Solid Tumor sensitive BRAF Inhibitor 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 F595L Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 T119S BRAF V600E colorectal cancer predicted - resistant BI-3406 Preclinical - Cell culture Actionable In a preclinical study, BI-3406 treatment failed to inhibit growth of colorectal cancer cells harboring BRAF V600E and BRAF T119S in culture (PMID: 32816843). 32816843
BRAF T119S BRAF V600E colorectal cancer predicted - sensitive LY3214996 Preclinical - Cell culture Actionable In a preclinical study, a colorectal cancer cell line harboring BRAF V600E and BRAF T119S was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). 31744895
BRAF G596V lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring BRAF G596V demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26200454). 26200454
BRAF G596V NRAS G13R colorectal cancer sensitive RAF Inhibitor (Pan) Cetuximab + LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). 28611205
BRAF G469L lung adenocarcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring BRAF G469L did not respond to Zelboraf (vemurafenib) therapy (PMID: 24035431). 24035431
BRAF class 2 pancreatic cancer predicted - sensitive RAF Inhibitor (Pan) KIN-2787 Preclinical - Cell culture Actionable In a preclinical study, KIN-2787 treatment led to inhibition of tumor growth in a pancreatic cell line xenograft model harboring a BRAF class 2 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). detail...
BRAF D594G melanoma sensitive RAF Inhibitor (Pan) Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited Erk phosphorylation, reduced growth, and induced mitochondrial depolarization and apoptosis in melanoma cells harboring BRAF D594G in culture, and inhibited tumor growth and induced regression in a cell line xenograft model (PMID: 18794803). 18794803
BRAF D594G melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor U0126 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF D594G demonstrated resistance to U0126 treatment in culture (PMID: 18794803). 18794803
BRAF D594G ampulla of Vater cancer predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Phase II Actionable In a Phase II trial (BEAVER), combination treatment with Mektovi (binimetinib) and Braftovi (encorafenib) led to a confirmed partial response in an ampullary cancer patient harboring BRAF D594G, who continued to be on treatment for 5.4 months (Annals of Oncology 32 (2021): S596; NCT03839342). detail...
BRAF D594G gastrointestinal system cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 4 patients with gastrointestinal system cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
BRAF D594G lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
BRAF D594G lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring BRAF D594G and TP53 H193L demonstrated stable disease for two months when treated with Mekinist (trametinib), but progressed after four months (PMID: 32540409). 32540409
BRAF D594G melanoma predicted - sensitive Ulixertinib Case Reports/Case Series Actionable In a clinical case study, Ulixertinib (BVD-523) treatment resulted in a histologic response allowing for surgical resection in a patient with metastatic melanoma harboring BRAF D594G (PMID: 35551160; NCT04566393). 35551160
BRAF D594G prostate cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with prostate cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). 31924734
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 D594G NRAS G12D melanoma sensitive RAF Inhibitor (Pan) TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive RAF Inhibitor (Pan) AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma decreased response BRAF Inhibitor 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 BRAF Inhibitor 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 decreased response RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF D594G NRAS G12D melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in a synergistic effect in melanoma cells harboring BRAF D594G and NRAS G12D, with decreased cell viability and Erk phosphorylation and increased apoptosis in culture (PMID: 35385748). 35385748
BRAF V600R melanoma sensitive RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF V600R melanoma sensitive RAF Inhibitor (Pan) 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 BRAF Inhibitor 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 BRAF Inhibitor Dabrafenib Case Reports/Case Series 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 BRAF Inhibitor PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). 27523909
BRAF T529I BRAF V600E Advanced Solid Tumor predicted - sensitive RAF Inhibitor (Pan) 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 T529I 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 in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I in culture (PMID: 20538618). 20538618
BRAF T529I BRAF V600E Advanced Solid Tumor predicted - resistant BRAF Inhibitor 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 T529I BRAF V600E Advanced Solid Tumor predicted - resistant BRAF Inhibitor 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 T529I BRAF V600E Advanced Solid Tumor predicted - sensitive BRAF Inhibitor 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 G469V lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G469V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G469V lung adenocarcinoma no benefit BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a previously treated lung adenocarcinoma patient harboring BRAF G469V demonstrated progression after 9 weeks of treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 32540409). 32540409
BRAF G469V lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma (HCC) and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions, complete response in the lung metastasis, and stability of the HCC following treatment with Nexavar (sorafenib) (PMID: 27388325). 27388325
BRAF G469V Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 BRAF Inhibitor 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 G469V osteosarcoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with osteosarcoma of the renal pelvis harboring BRAF G469V (PMID: 31924734; NCT02465060). 31924734
BRAF G469V NRAS Q61K melanoma no benefit BRAF Inhibitor 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 NRAS Q61K melanoma sensitive BRAF Inhibitor 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 RAF Inhibitor (Pan) 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 BRAF Inhibitor 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 RAF Inhibitor (Pan) 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 L485W gallbladder cancer sensitive Ulixertinib Case Reports/Case Series Actionable In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a complete response lasting almost 1 year in a gallbladder cancer patient harboring BRAF L485W (PMID: 29247016, PMID: 29247021). 29247021 29247016
BRAF K601E melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) treatment resulted in a partial response in a patient with metastatic melanoma harboring BRAF K601E, increased inhibition of Erk1/2 phosphorylation in a melanoma cell line expressing BRAF K601E in culture, and increased tumor growth inhibition in a patient-derived xenograft (PDX) model compared to Mekinist (trametinib) alone (PMID: 30248172). 30248172
BRAF K601E pancreatic endocrine carcinoma predicted - resistant BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 31158244). 31158244
BRAF K601E colorectal cancer resistant RAF Inhibitor (Pan) Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment in combination with Zelboraf (vemurafenib) did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E melanoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in transient disease stabilization followed by metastatic progression in a patient with metastatic melanoma harboring BRAF K601E (PMID: 31182949). 31182949
BRAF K601E melanoma no benefit BRAF Inhibitor Dabrafenib Phase I Actionable In a Phase I trial, no responses were demonstrated among three melanoma patients with non-V600 BRAF mutations, including two patients harboring BRAF K601E, following treatment with Tafinlar (dabrafenib), compared to a confirmed response rate of 50% in patients harboring BRAF V600 mutations (PMID: 22608338). 22608338
BRAF K601E colorectal cancer resistant Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E pancreatic endocrine carcinoma predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 31158244). 31158244
BRAF K601E lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF K601E, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
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 colorectal cancer resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E Advanced Solid Tumor conflicting RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture 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 RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 RAF Inhibitor (Pan) 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 lung adenocarcinoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response lasting at least nine months with near-complete tumor regression in a patient with lung adenocarcinoma harboring BRAF K601E (PMID: 34590045). 34590045
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient harboring 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 predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series 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 colorectal cancer predicted - sensitive BRAF Inhibitor PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment resulted in partial inhibition of tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E melanoma predicted - sensitive RAF Inhibitor (Pan) Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment induced limited apoptosis and inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). 18794803
BRAF K601E melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor U0126 Preclinical - Cell culture Actionable In a preclinical study, U0126 treatment inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). 18794803
BRAF K601E colorectal cancer sensitive BRAF Inhibitor Cetuximab + PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E prostate adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in a near partial response in a patient with prostate adenocarcinoma harboring BRAF K601E until disease progression at 9.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF S363F BRAF K601E 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 S363F BRAF K601E 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 S363F BRAF K601E 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 S363F BRAF K601E melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 S363F BRAF K601E melanoma sensitive BRAF Inhibitor 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 S363F BRAF K601E melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) 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 S363F BRAF K601E melanoma sensitive BRAF Inhibitor 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 MAP2K1 V211D colon cancer predicted - resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Panitumumab Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Cetuximab Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer sensitive MEK inhibitor (Pan) MAP855 Preclinical - Pdx Actionable In a preclinical study, MAP955 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF L597K melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) resulted in a partial response and clinical improvement in a patient with metastatic melanoma harboring BRAF L597K (PMID: 33560788). 33560788
BRAF P731T Advanced Solid Tumor no benefit RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 P731T (PMID: 29320312; NCT02091141). 29320312
BRAF V47_D380del melanoma predicted - resistant BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a melanoma patient developed progressive disease after initial response to Tafinlar (dabrafinib) and Mekinist (trametinib) combination treatment, BRAF V47_D380del was identified as an acquired mutation in the progressing lesion along with mutations presented in both primary and progressing lesions, including BRAF V600E, PTEN G129E, CDKN2A/B loss, and TERT promoter mutations (PMID: 29171936). 29171936
BRAF V47_D380del BRAF V600E melanoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, expression of BRAF V47_D380del in a melanoma cell line harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 29605720). 29605720
BRAF V47_D380del BRAF V600E colorectal cancer predicted - resistant BRAF Inhibitor Alpelisib + Cetuximab + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 24 weeks to Alpelisib (BYL719), Erbitux (cetuximab), and Braftovi (encorafenib) combination treatment, BRAF V47_D380del (reported as deletion of exons 2-8) was identified as an acquired mutation in peritoneal metastasis at the time of progression (PMID: 28951457). 28951457
BRAF N486_P490del melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma predicted - sensitive BRAF Inhibitor GDC0879 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). 26996308
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) LY3009120 + Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated inhibition of Erk phosphorylation and greater inhibition of tumor growth when treated with the combination of Mekinist (trametinib) and LY3009120 compared to either agent alone (PMID: 34011980). 34011980
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer sensitive RAF Inhibitor (Pan) 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 BRAF Inhibitor 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 N486_P490del ovarian cancer sensitive RAF Inhibitor (Pan) AZ628 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). 26996308
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive RAF Inhibitor (Pan) LY3009120 Preclinical - Pdx & cell culture Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with LY3009120 (PMID: 34011980). 34011980
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series 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 pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx Actionable In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with Mekinist (trametinib) (PMID: 34011980). 34011980
BRAF N486_P490del melanoma sensitive RAF Inhibitor (Pan) AZ628 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). 26996308
BRAF N486_P490del lymphatic system cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). 32991018
BRAF N486_P490del ovarian cancer predicted - sensitive BRAF Inhibitor GDC0879 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). 26996308
BRAF N486_P490del ovarian cancer sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of a melanoma cell line harboring BRAF N486_P490del in culture (PMID: 26996308). 26996308
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 ovarian cancer resistant RAF Inhibitor (Pan) 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 resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26996308). 26996308
BRAF N486_P490del pancreatic cancer predicted - sensitive BRAF Inhibitor Dabrafenib Case Reports/Case Series Actionable In a clinical case study, a patient with pancreatic cancer harboring BRAF N486_P490del had a partial response when treated with Tafinlar (dabrafenib), demonstrating a decrease in both the size of the primary and metastatic lesions and response duration of 6 months (PMID: 31519698). 31519698
BRAF N486_P490del melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H Advanced Solid Tumor sensitive BRAF Inhibitor GDC0879 Preclinical - Biochemical Actionable In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H BRAF V600E Advanced Solid Tumor sensitive BRAF Inhibitor GDC0879 Preclinical - Biochemical Actionable In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H BRAF V600E Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). 26996308
BRAF G469A lung adenocarcinoma resistant Ravoxertinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409). 32540409
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 G469A lung non-small cell carcinoma resistant RAF Inhibitor (Pan) 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 lung non-small cell carcinoma resistant RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G469A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G469A lung adenocarcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF G469A lung adenocarcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF G469A, who remained on therapy for 20.4 months without progression (PMID: 31924734; NCT02465060). 31924734
BRAF G469A lung adenocarcinoma resistant RAF Inhibitor (Pan) MLN2480 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with MLN2480 (TAK-580) in culture (PMID: 32540409). 32540409
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 lung adenocarcinoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). 32540409
BRAF G469A lung non-small cell carcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 lung adenocarcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF G469A lung adenocarcinoma resistant MK-8353 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with MK-8353 in culture (PMID: 32540409). 32540409
BRAF G469A lung adenocarcinoma resistant Ulixertinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ulixertinib (BVD-523) in culture (PMID: 32540409). 32540409
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 lung non-small cell carcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) 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 lung non-small cell carcinoma conflicting MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) 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 lung adenocarcinoma resistant BRAF Inhibitor Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Tafinlar (dabrafenib) in culture (PMID: 32540409). 32540409
BRAF G469A lung non-small cell 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 Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 RAF Inhibitor (Pan) 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 lung non-small cell carcinoma sensitive BRAF Inhibitor 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 lung adenocarcinoma resistant LY3214996 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with LY3214996 in culture (PMID: 32540409). 32540409
BRAF G469A melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in symptom improvement, reduced lymph node size, and decreased LDH levels in a patient with metastatic melanoma harboring BRAF G469S, with progression observed after three months (PMID: 31569065). 31569065
BRAF G469A lung non-small cell carcinoma sensitive BRAF Inhibitor 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 adenocarcinoma sensitive BRAF Inhibitor BGB-283 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with Lifirafenib (BGB-283) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF G469A lung adenocarcinoma sensitive BRAF Inhibitor LXH 254 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF G469A melanoma sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of melanoma cells harboring BRAF G469A in culture (PMID: 30559419). 30559419
BRAF G469A lung adenocarcinoma sensitive BRAF Inhibitor 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 lung non-small cell 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 BRAF L584P melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in decrease in metastatic lesions and a partial response with 94% reduction at three months and continued metabolic response at six months in a patient with metastatic melanoma harboring BRAF G469A and BRAF L584P (PMID: 31569065). 31569065
BRAF G469A BRAF W604C lung adenocarcinoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in stable disease indicated by decreased tumor density and disappearance of some metastatic lesions lasting 15 months in a patient with lung adenocarcinoma harboring BRAF G469A and W604C (PMID: 30926357). 30926357
BRAF I463W BRAF V600E melanoma resistant BRAF Inhibitor Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF V600E and expressing BRAF I463W or expressing BRAF V600E and I463W in cis demonstrated resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). 31925410
BRAF K601T Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 L514V breast cancer resistant BRAF Inhibitor 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 RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response 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 predicted - sensitive RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) 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 melanoma predicted - sensitive BGB3290 Preclinical - Cell culture Actionable In a preclinical study, BGB3290 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E ganglioglioma resistant BRAF Inhibitor Dabrafenib Case Reports/Case Series 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 BRAF Inhibitor 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 L597S melanoma predicted - sensitive BRAF Inhibitor Dabrafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture, but did not result in tumor shrinkage as a single agent in a melanoma patient-derived xenograft (PDX) model harboring BRAF L597S (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive BRAF Inhibitor 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 melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive RAF Inhibitor (Pan) LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of melanoma cells harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, Cotellic (cobimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S Advanced Solid Tumor sensitive RAF Inhibitor (Pan) Vemurafenib Preclinical Actionable In a preclinical study, treatment of cells expressing BRAF L597S with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF L597S melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S 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 L597S (PMID: 22798288). 22798288
BRAF L597S melanoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 75% (8/12) subcutaneous tumors in one patient-derived xenograft (PDX) model harboring BRAF L597S that also harbored a BRAF variant of unknown significance, BRAF R239Q, however, was not sufficient to induce tumor shrinkage in a second PDX model with BRAF L597S, resulting only in tumor growth delay (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 89% (17/19) of tumors in a patient-derived xenograft (PDX) model harboring BRAF L597S, and treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a objective response with 34% tumor shrinkage in the patient from which the PDX model was derived from (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive BRAF Inhibitor Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive BRAF Inhibitor 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 melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor TAK-733 Phase I Actionable In a Phase I trial, one metastatic melanoma patient carrying a BRAF L597S mutation, had a partial response to the MEK inhibitor, TAK-733 (PMID: 22798288). 22798288
BRAF R239Q BRAF L597S melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 R239Q BRAF L597S melanoma sensitive BRAF Inhibitor 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 R239Q BRAF L597S 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 R239Q BRAF L597S melanoma sensitive BRAF Inhibitor 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 class 1 melanoma predicted - sensitive RAF Inhibitor (Pan) KIN-2787 Preclinical - Cell line xenograft Actionable In a preclinical study, KIN-2787 treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring a BRAF class 1 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). detail...
BRAF T529M BRAF V600E 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 T529M BRAF V600E Advanced Solid Tumor predicted - resistant BRAF Inhibitor 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 T529M BRAF V600E Advanced Solid Tumor predicted - sensitive BRAF Inhibitor 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 T529M BRAF V600E Advanced Solid Tumor predicted - sensitive RAF Inhibitor (Pan) 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 T529M BRAF V600E Advanced Solid Tumor predicted - resistant BRAF Inhibitor 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 V600L mucosal melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in complete remission in a patient with unresectable hypopharyngeal mucosal melanoma harboring BRAF V600L (PMID: 35709404). 35709404
BRAF K601N lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 2 patients harboring BRAF K601N, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF K601N lung non-small cell carcinoma predicted - sensitive BRAF Inhibitor LTT462 + LXH 254 Case Reports/Case Series Actionable In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF K601N achieving an unconfirmed PR (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). detail...
BRAF K601N chronic lymphocytic leukemia sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of chronic lymphocytic leukemia cells harboring BRAF K601N in culture (PMID: 30559419). 30559419
BRAF K601N hematologic cancer sensitive RAF Inhibitor (Pan) 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). 26732095
BRAF K601N Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 wild-type melanoma predicted - sensitive BRAF Inhibitor RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited the growth of melanoma tumors orthotopically implanted in mice, including tumors wild-type for BRAF (PMID: 22351689). 22351689
BRAF wild-type melanoma predicted - sensitive BRAF Inhibitor 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 wild-type colon cancer predicted - sensitive Cetuximab Guideline Actionable Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). detail...
BRAF wild-type colon cancer predicted - sensitive Panitumumab Guideline Actionable Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). detail...
BRAF wild-type melanoma resistant BRAF Inhibitor GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells in cell culture, cell line xenograft models, and patient-derived xenograft models (PMID: 19276360). 19276360
BRAF wild-type melanoma no benefit RAF Inhibitor (Pan) Vemurafenib Preclinical - Patient cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). 23715574
BRAF wild-type melanoma decreased response MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a BRAF wild-type melanoma cell line demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF wild-type rectum cancer predicted - sensitive Cetuximab Guideline Actionable Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). detail...
BRAF wild-type rectum cancer predicted - sensitive Panitumumab Guideline Actionable Vectibix (panitumumab) is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). detail...
BRAF wild-type melanoma resistant BRAF Inhibitor PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 did not inhibit growth of BRAF wild-type melanoma cells in culture or in cell line xenograft models (PMID: 18287029). 18287029
BRAF wild-type high grade glioma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Everolimus + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and Selumetinib (AZD6244) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). 27217440
BRAF wild-type melanoma predicted - sensitive Nivolumab Phase III Actionable In a Phase III trial (CheckMate-066), Opdivo (nivolumab) treatment resulted in improved overall survival and response compared to treatment with Deticene (dacarbazine) in melanoma patients with wild-type BRAF, including a 3-year overall survival (OS) rate of 51.2% vs. 21.6%, a median OS of 37.5 months vs. 11.2 months, a complete response in 19% (40/210) vs. 1.4% (3/208), and a partial response in 23.8% (50/210) vs. 13% (27/208), respectively (PMID: 30422243; NCT01721772). 30422243
BRAF wild-type Advanced Solid Tumor resistant BRAF Inhibitor BGB-283 Preclinical - Cell culture Actionable In a preclinical study, a variety of BRAF wild-type tumor cell lines were insensitive to BGB-283 in culture (PMID: 26208524). 26208524
BRAF wild-type melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase II Actionable In a Phase II trial, a favorable response rate to Koselugo (selumetinib) was observed in BRAF-mutant, but not BRAF wild-type, melanoma patients (PMID: 22048237). 22048237
BRAF wild-type melanoma no benefit BRAF Inhibitor Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). 23715574
BRAF wild-type melanoma predicted - sensitive RAF Inhibitor (Pan) Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). 23715574
BRAF wild-type lung non-small cell carcinoma resistant BRAF Inhibitor GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells in culture and in patient-derived xenograft models (PMID: 19276360). 19276360
BRAF wild-type thyroid gland cancer sensitive CLM3 Preclinical Actionable In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression, in BRAF wild-type thyroid cancer cells in culture (PMID: 24423321). 24423321
BRAF wild-type melanoma sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, BRAF wild-type melanoma cells demonstrated decreased cell viability when treated with Ibrance (palbociclib) in culture (PMID: 27488531). 27488531
BRAF wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase I Actionable In a Phase I study, 10% (4/39) of wild-type BRAF melanoma patients had a partial response to Mekinist (trametinib) (PMID: 22805292; NCT00687622). 22805292
BRAF wild-type NRAS mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 83% (5/6) of melanoma patients harboring NRAS mutations and wild-type BRAF (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma sensitive RAF Inhibitor (Pan) TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma resistant BRAF Inhibitor PLX7904 Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to PLX7904 in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive RAF Inhibitor (Pan) AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS wild-type melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 44% (4/9) and partial response in 22% (2/9) of melanoma patients carrying wild-type BRAF and NRAS (PMID: 26169970). 26169970
BRAF wild-type NRAS wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Buparlisib 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 with wild-type BRAF and wild-type NRAS in culture (PMID: 27307593). 27307593
BRAF wild-type NRAS wild-type melanoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, BRAF and NRAS wild-type melanoma cells were resistant to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF wild-type NRAS Q61K melanoma resistant BRAF Inhibitor GDC0879 Preclinical - Pdx Actionable In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells harboring NRAS Q61K in patient-derived xenograft models (PMID: 19276360). 19276360
BRAF G464V Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 G464V lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G464V (PMID: 31924734; NCT02465060). 31924734
BRAF L485_P490del Advanced Solid Tumor predicted - sensitive RAF Inhibitor (Pan) LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited phosphorylation of Mek and Erk in transformed cells expressing BRAF L485_P490del in culture (PMID: 26732095). 26732095
BRAF L485_P490del Advanced Solid Tumor predicted - resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) failed to inhibit phosphorylation of Mek and Erk in transformed cells expressing BRAF L485_P490del in culture (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive RAF Inhibitor (Pan) LY3009120 Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to LY3009120 in both culture and xenograft models, resulting in significant tumor regression and inhibition of MEK and ERK phosphorylation (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to Mekinist (trametinib), resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma resistant BRAF Inhibitor Dabrafenib Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was resistant to Tafinlar (dabrafenib) (PMID: 26732095). 26732095
BRAF N486_T491delinsK lymphatic system cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Case Reports/Case Series Actionable In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with Langerhans cell histiocytosis harboring BRAF N486_T491delinsK (PMID: 30867592; NCT01953926). 30867592
BRAF N486_T491delinsK Advanced Solid Tumor predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, Cotellic (cobimetinib) inhibited viability of transformed cells expressing BRAF N486_T491delinsK in culture (PMID: 30867592). 30867592
BRAF N581S lung adenocarcinoma predicted - sensitive PF-00477736 + PF3644022 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 N581S female reproductive organ cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecologic cancer harboring BRAF N581S (PMID: 31924734; NCT02465060). 31924734
BRAF N581S lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF N581S (PMID: 31924734; NCT02465060). 31924734
BRAF N581S lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF N581S, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF N581S Advanced Solid Tumor no benefit RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 G469S gallbladder cancer predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Phase II Actionable In a Phase II trial (BEAVER), combination treatment with Mektovi (binimetinib) and Braftovi (encorafenib) led to stable disease in a gallbladder cancer patient harboring BRAF D594N, with a treatment duration of 4.4 months (Annals of Oncology 32 (2021): S596; NCT03839342). detail...
BRAF G469S melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Case Reports/Case Series Actionable In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy resulted in an unconfirmed partial response in a patient with melanoma harboring BRAF G469S (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). detail...
BRAF D287H NRAS Q61K melanoma predicted - sensitive BRAF Inhibitor LXH 254 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line harboring BRAF D287H and NRAS Q61K was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model of melanoma (PMID: 33355204). 33355204
BRAF T310I breast cancer predicted - resistant BRAF Inhibitor Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) treatment resulted in increased Erk phosphorylation in breast cancer cells expressing BRAF T310I in culture (PMID: 31158244). 31158244
BRAF G596R Advanced Solid Tumor no benefit RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 G596R (PMID: 29320312; NCT02091141). 29320312
BRAF G596R colorectal cancer predicted - sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF G596R demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). 30559419
BRAF G596R colorectal cancer sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28947956). 28947956
BRAF G596R colorectal cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of colorectal cancer cells harboring BRAF G596R in culture (PMID: 30104724). 30104724
BRAF G596R colorectal cancer resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Erk and Mek in a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). 28783719
BRAF G596R lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G596R, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G596R colorectal cancer 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 colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). 28783719
BRAF G596R PIK3CA E545K colorectal cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells harboring both BRAF G596R and PIK3CA E545K in culture (PMID: 26243863). 26243863
BRAF G596R PIK3CA E545K colorectal cancer resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF G596R and PIK3CA E545K did not demonstrate sensitivity to Zelboraf (vemurafenib) treatment in culture (PMID: 22180495). 22180495
BRAF V504_R506dup Advanced Solid Tumor resistant RAF Inhibitor (Pan) Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Nexavar (sorafenib) in culture (PMID: 30575814). 30575814
BRAF V504_R506dup Advanced Solid Tumor resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Cell culture Actionable In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Mekinist (trametinib) in culture (PMID: 30575814). 30575814
BRAF V504_R506dup Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Zelboraf (vemurafenib) in culture (PMID: 30575814). 30575814
BRAF G466V lung non-small cell carcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 lung adenocarcinoma sensitive BRAF Inhibitor 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 lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) 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 lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G466V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G466V colorectal cancer sensitive BRAF Inhibitor Cetuximab + PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V colorectal cancer resistant BRAF Inhibitor PLX8394 Preclinical - Pdx Actionable In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
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 sensitive Cetuximab Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V lung non-small cell 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 lung cancer predicted - sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells harboring BRAF G466V demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). 30559419
BRAF G466V colorectal cancer sensitive RAF Inhibitor (Pan) Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). 30559419
BRAF G466V lung non-small cell carcinoma sensitive RAF Inhibitor (Pan) 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 colorectal cancer predicted - sensitive Irinotecan + Panitumumab Case Reports/Case Series 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 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 Advanced Solid Tumor no benefit RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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
BRAF G466V lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G466V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V lung non-small cell 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 colorectal cancer predicted - resistant RAF Inhibitor (Pan) 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 predicted - resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). 30559419
BRAF G466V lung non-small cell 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 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 Advanced Solid Tumor no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with tumor of unknown primary harboring BRAF G464V (PMID: 31924734; NCT02465060). 31924734
BRAF G466V NRAS Q61K lung non-small cell 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 S365L BRAF V600E lung papillary adenocarcinoma predicted - sensitive RAF Inhibitor (Pan) Bevacizumab + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) and Avastin (bevacizumab) combination treatment resulted in regression of some brain lesions while others remained stable in a patient with lung papillary carcinoma harboring BRAF V600E and S365L (PMID: 34178685). 34178685
BRAF S365L BRAF V600E lung papillary adenocarcinoma predicted - resistant BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung papillary carcinoma harboring BRAF V600E who previously responded to Tafinlar (dabrafenib) and Mekinist (trametinib) treatment was found to have acquired BRAF S365L upon disease progression (PMID: 34178685). 34178685
BRAF mutant colorectal cancer sensitive RAF Inhibitor (Pan) 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 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 RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) 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 colorectal cancer sensitive RAF Inhibitor (Pan) Belvarafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Belvarafenib (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 Advanced Solid Tumor sensitive BRAF Inhibitor 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 lung non-small cell carcinoma predicted - sensitive unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant colorectal cancer predicted - sensitive RAF Inhibitor (Pan) 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 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 Advanced Solid Tumor predicted - sensitive RAF Inhibitor (Pan) 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 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 Advanced Solid Tumor predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Phase II Actionable In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring BRAF non-V600E mutations, resulting in an objective response rate of 12.5% (1/8), BRAF mutations including class 1 (n=1), class 2 (n=3), and class 3 (n=5) (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). detail...
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 lung non-small cell carcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
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 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 melanoma sensitive RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) 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 lymphoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). 31924734
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 RAF Inhibitor (Pan) 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 lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF non-V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
BRAF mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study Actionable In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). 31367539
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 Tubastatin A Preclinical Actionable In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). 25957812
BRAF mutant melanoma sensitive 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 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 colorectal cancer sensitive BRAF Inhibitor Alpelisib + Cetuximab + Encorafenib 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 Advanced Solid Tumor predicted - sensitive BRAF Inhibitor LXH 254 Case Reports/Case Series Actionable In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). 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 mutant Advanced Solid Tumor predicted - sensitive PF-00477736 + PF3644022 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 BRAF Inhibitor Buparlisib + Encorafenib 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 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 colon cancer predicted - sensitive PF-00477736 + PF3644022 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 RAF Inhibitor (Pan) AZ628 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). 26351322
BRAF mutant Advanced Solid Tumor sensitive BRAF Inhibitor RAF709 Preclinical - Cell culture 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 splenic marginal zone lymphoma not applicable N/A Guideline Diagnostic BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org). detail...
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 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 melanoma predicted - sensitive RAF Inhibitor (Pan) UNC2025 + Vemurafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852). 30482852
BRAF mutant thyroid gland cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase I Actionable In a Phase I study, Koselugo (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 (PMID: 23406027). 23406027
BRAF mutant colorectal cancer no benefit BRAF Inhibitor 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 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 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 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 gland cancer sensitive RAF Inhibitor (Pan) Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant colorectal cancer predicted - sensitive SY-5609 Preclinical - Pdx Actionable In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). detail...
BRAF mutant Advanced Solid Tumor no benefit RAF Inhibitor (Pan) LY3009120 Case Reports/Case Series Actionable In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116). 31645440
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 BRAF Inhibitor 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 melanoma sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). 27307593
BRAF mutant colorectal cancer sensitive RAF Inhibitor (Pan) MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant melanoma sensitive BRAF Inhibitor 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 colorectal cancer predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Panitumumab + Trametinib 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 melanoma predicted - sensitive RAF Inhibitor (Pan) Belvarafenib Phase I Actionable In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in a patients with BRAF-mutant melanoma in a dose escalation study, and partial response in 33% (2/6) of BRAF-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). detail...
BRAF mutant lung non-small cell 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 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 lung non-small cell carcinoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 Advanced Solid Tumor no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF mutant melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Buparlisib 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 melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Case Reports/Case Series Actionable In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). 22048237
BRAF mutant colorectal cancer decreased response BRAF Inhibitor 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 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 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 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 colorectal cancer sensitive BRAF Inhibitor Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). 28363909
BRAF mutant colorectal cancer 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 mut TP53 wild-type Advanced Solid Tumor predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Pimasertib + SAR405838 Phase I Actionable In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). 30585255
BRAF mut TP53 wild-type melanoma sensitive KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (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 BRAF Inhibitor CGM097 + Encorafenib 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 BRAF Inhibitor CGM097 + Dabrafenib + Navitoclax + 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 mut melanoma sensitive Lenvatinib Phase I Actionable In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). 26169970
BRAF mut NRAS mut melanoma predicted - sensitive 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 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 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 RAF Inhibitor (Pan) SAR260301 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). 27196754
BRAF mut PTEN loss melanoma sensitive GSK2636771 + Pembrolizumab Preclinical Actionable In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). 26645196
BRAF mut PTEN loss melanoma sensitive SAR260301 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 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 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 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 no benefit BRAF Inhibitor Encorafenib + GSK2636771 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 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 PTEN wild-type melanoma no benefit BRAF Inhibitor AZD6482 + Encorafenib 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 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 Binimetinib + GSK2636771 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 GSK2636771 + NVP-AEW541 Preclinical Actionable In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + 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 inact mut melanoma no benefit BRAF Inhibitor Alpelisib + Encorafenib 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 Alpelisib + AZD6482 Preclinical Actionable In a preclinical study, AZD6482 and Alpelisib (BYL719) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BRAF Inhibitor Alpelisib + Encorafenib + GSK2636771 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 Alpelisib + 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 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 Alpelisib + AZD6482 + Binimetinib 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 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 MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + GSK2636771 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 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 sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Alpelisib + AZD6482 + Binimetinib + Encorafenib Preclinical Actionable In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive GSK2636771 + 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 BRAF Inhibitor Encorafenib + GSK2636771 + 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 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 BRAF Inhibitor 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 BRAF Inhibitor Encorafenib + unspecified IGF-1R antibody Preclinical Actionable In a preclinical study, combination treatment consists of Encorafenib (LGX818) and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive 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 sensitive GSK2636771 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive NVP-AEW541 + Pictilisib Preclinical Actionable In a preclinical study, Pictilisib (GDC-0941) and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive BRAF Inhibitor Alpelisib + AZD6482 + Encorafenib 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 BRAF Inhibitor AZD6482 + Encorafenib 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 BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor AZD6482 + Binimetinib + Encorafenib + 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 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 BRAF Inhibitor Encorafenib + GSK2636771 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 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 BRAF Inhibitor AZD6482 + Encorafenib + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 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 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 no benefit Alpelisib + 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 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 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 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 TP53 mut colorectal cancer sensitive BRAF Inhibitor Alpelisib + Dabrafenib + Erlotinib + Navitoclax 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 PIK3CA wild-type colorectal cancer predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor TAK-733 Preclinical - Pdx & cell culture Actionable In a preclinical study, mutations in BRAF, KRAS, or NRAS were associated with sensitivity to TAK-733 in colorectal cancer cell lines in culture, and patient-derived xenograft models harboring KRAS or BRAF mutations with wild-type PIK3CA demonstrated a trend toward higher tumor growth inhibition following TAK-733 treatment (PMID: 26439693). 26439693
BRAF mut IDH1 wild-type glioblastoma predicted - sensitive Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, 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 who 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 IDH1 wild-type glioblastoma predicted - sensitive Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, 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 who 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 G464R Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cetuximab + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) and Erbitux (cetuximab) synergistically inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q lung cancer sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in a lung cancer patient harboring BRAF L597Q (PMID: 29247021). 29247021
BRAF L597Q Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 L597Q (PMID: 29320312; NCT02091141). 29320312
BRAF L597Q Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 L597Q (PMID: 26343582). 26343582
BRAF L597Q colon adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Preclinical - Patient cell culture Actionable In a preclinical study, Koselugo (selumetinib) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q colon adenocarcinoma predicted - sensitive Sapitinib Preclinical - Patient cell culture Actionable In a preclinical study, Sapitinib (AZD8931) inhibited growth of tumor cells derived from the metachronous para-aortal lymph node metastasis harboring BRAF L597Q, which was resected from a patient with colon adenocarcinoma (PMID: 31704811). 31704811
BRAF L597Q FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma predicted - resistant Futibatinib Case Reports/Case Series Actionable In a clinical case study, acquisition of BRAF L597Q was identified in an intrahepatic cholangiocarcinoma patient harboring FGFR2 H167_N173del and FGFR2 L618F who developed resistance to treatment with Futibatinib (TAS-120) (PMID: 33926920). 33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma no benefit LY3214996 Case Reports/Case Series Actionable In a clinical case study, LY3214996 treatment led to progressive disease after 2 months in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). 33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 N550K FGFR2 L618F NRAS Q61K intrahepatic cholangiocarcinoma predicted - resistant LY3214996 Case Reports/Case Series Actionable In a clinical case study, acquired NRAS Q61K and FGFR2 N550K mutations were identified following progression on LY3214996 in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). 33926920
BRAF G469R NRAS Q61K melanoma resistant RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) 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 T529N BRAF V600E Advanced Solid Tumor resistant BRAF Inhibitor 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 T529N BRAF V600E Advanced Solid Tumor resistant BRAF Inhibitor 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 T529N 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 and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). 20538618
BRAF T529N BRAF V600E Advanced Solid Tumor conflicting RAF Inhibitor (Pan) 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 T529N BRAF V600E Advanced Solid Tumor resistant BRAF Inhibitor 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 G534D NRAS Q61L melanoma resistant RAF Inhibitor (Pan) Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, expression of BRAF G534D in a melanoma cell line harboring NRAS Q61L conferred resistance to treatment with Belvarafenib (HM95573) in culture (PMID: 33953400). 33953400
BRAF V487_P492delinsA pancreatic cancer sensitive RAF Inhibitor (Pan) 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 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 resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer resistant BRAF Inhibitor 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 fusion pilocytic astrocytoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Guideline Actionable Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring a BRAF fusion (NCCN.org). detail...
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 fusion prostate cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring a BRAF fusion (PMID: 31924734; NCT02465060). 31924734
BRAF G466E melanoma decreased response BRAF Inhibitor Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF G466E melanoma decreased response RAF Inhibitor (Pan) 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 melanoma decreased response BRAF Inhibitor 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 RAF Inhibitor (Pan) 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 sensitive RAF Inhibitor (Pan) 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 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 G606E Advanced Solid Tumor no benefit RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an 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 G606E (PMID: 29320312; NCT02091141). 29320312
BRAF N581D lung non-small cell 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 R509H BRAF V600E Advanced Solid Tumor sensitive RAF Inhibitor (Pan) Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) reduced Mek phosphorylation in transformed cells expressing BRAF V600E and R509H in culture (PMID: 26996308). 26996308
BRAF R509H BRAF V600E Advanced Solid Tumor sensitive BRAF Inhibitor GDC0879 Preclinical - Biochemical Actionable In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF V600E and R509H in culture (PMID: 26996308). 26996308
BRAF L505H melanoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical Actionable In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). 24283590
BRAF L505H BRAF V600E melanoma predicted - resistant RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series 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 V600X lung non-small cell carcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Guideline Actionable The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation, or as subsequent therapy in patients harboring BRAF V600 mutations that have not received prior BRAF/MEK inhibitor therapy (PMID: 32169226; ESMO.org). 32169226 detail...
BRAF V600X melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Nivolumab + Trametinib Phase II Actionable In a Phase II trial, combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Opdivo (nivolumab) resulted in an objective response rate (ORR) of 92% (24/27, 3 CR, 21 PR) in patients with MEK inhibitor-naive, BRAF V600-mutated melanoma, with a median progression-free survival of 8.5 mos, ORR was 88% (14/16) and 100% (10/10) in PD1 refractory or naive patients, 57% (4/7) of patients with brain metastasis achieved intracranial response (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9520; NCT02910700). detail...
BRAF V600X melanoma sensitive BRAF Inhibitor 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 RAF Inhibitor (Pan) 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 colorectal cancer sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 Buparlisib + 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 thyroid gland cancer predicted - sensitive RAF Inhibitor (Pan) 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 skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Atezolizumab + Cobimetinib + Vemurafenib Guideline Actionable Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) combination therapy is included in guidelines as a preferred first-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + KRT-232 + Trametinib Phase I Actionable In a Phase I trial, the combination therapy of KRT-232 (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 skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Cotellic (cobimetinib) plus Zelboraf (vemurafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X colorectal cancer sensitive RAF Inhibitor (Pan) Cetuximab + Vemurafenib 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 skin melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Guideline Actionable Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X skin melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Mektovi (binimetinib) plus Braftovi (encorafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X Advanced Solid Tumor predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Belvarafenib + Cobimetinib Phase I Actionable In a Phase Ib trial, combination treatment with Belvarafenib (HM95573) and Cotellic (cobimetinib) was well-tolerated and demonstrated safety, and led to a confirmed partial response in 33.3% (3/9) solid tumor patients harboring BRAF V600 mutations (Annals of Oncology 32 (2021): S595; NCT03839342). detail...
BRAF V600X cholangiocarcinoma sensitive RAF Inhibitor (Pan) 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 lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Phase II Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations (PMID: 31959346; NCT02304809). 31959346
BRAF V600X Advanced Solid Tumor predicted - sensitive BRAF Inhibitor BGB-283 Phase I Actionable In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 5 patients with BRAF V600E/K-mutant melanoma, 2 patients with BRAF V600E-mutant thyroid cancer, and 1 patient with BRAF V600E-mutant low-grade serous ovarian carcinoma, complete response in 1.9% (1/53), in a patient with melanoma, and stable disease in 50.9% (27/53) (PMID: 32182156; NCT02610361). 32182156
BRAF V600X melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 melanoma sensitive RAF Inhibitor (Pan) Buparlisib + 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 melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib + Pembrolizumab Phase I Actionable In a Phase I trial (IMMU-Target), Mektovi (binimetinib), Braftovi (encorafenib), and Keytruda (pembrolizumab) demonstrated safety and preliminary efficacy in treatment naive patients with advanced melanoma harboring BRAF V600 mutations, resulting in an overall response rate of 64% (9/14), with a 12-month progression-free survival rate of 37.5% (n=8) and 60% (n=6) at the two tested dose levels, respectively (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9532; NCT02902042). detail...
BRAF V600X low grade glioma predicted - sensitive BRAF Inhibitor Dabrafenib Phase Ib/II Actionable In a Phase I/II trial, Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in an objective response rate of 44% (14/32, 1 complete response, 13 partial response) and a disease control rate of 78% (25/32), with a median duration of response of 26 months in pediatric patients with BRAF V600-mutant low-grade gliomas (PMID: 31811016; NCT01677741). 31811016
BRAF V600X melanoma sensitive RAF Inhibitor (Pan) Atezolizumab + Vemurafenib Phase Ib/II Actionable In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab) and Zelboraf (vemurafenib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 76.5% (13/17), with a complete response in 17.6% (3/17), a median progression-free survival of 10.9 months, a median overall survival of 46.2 months, and median duration of confirmed response of 10.6 months (PMID: 31171876; NCT01656642). 31171876
BRAF V600X melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Spartalizumab + Trametinib Phase III Actionable In a Phase III trial (COMBI-i), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Spartalizumab (PDR001) resulted in an objective response rate of 78% (28/36, 16 complete, 12 partial), disease control rate of 94% (34/36), and median progression-free survival of 23 months in patients with BRAF V600-mutant metastatic melanoma, including 29 patients (81%) harboring BRAF V600E and 4 patients (11%) harboring BRAF V600K (PMID: 33020648; NCT02967692). 33020648
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib 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 RAF Inhibitor (Pan) Atezolizumab + Cobimetinib + Vemurafenib Phase Ib/II Actionable In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 71.8% (28/39), with a complete response in 20.5% (8/39), a median progression-free survival of 12.9 months, a median overall survival not yet reached, and median duration of confirmed response of 17.4 months (PMID: 31171876; NCT01656642). detail... 31171876
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Atezolizumab + Cobimetinib + Vemurafenib FDA approved Actionable In a Phase III trial (IMspire150) that supported FDA approval, addition of Tecentriq (atezolizumab) to Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy significantly improved progression-free survival (15.1 vs 10.6 months, HR=0.78, p=0.025) compared to control in patients with advanced or metastatic melanoma harboring BRAF V600 mutations (PMID: 32534646; NCT02908672). 32534646 detail...
BRAF V600X skin melanoma sensitive RAF Inhibitor (Pan) Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X ganglioglioma predicted - sensitive BRAF Inhibitor Dabrafenib Case Reports/Case Series Actionable In a Phase I/II trial, Tafinlar (dabrafenib) treatment resulted in a partial response in a pediatric patient with BRAF V600-mutant ganglioglioma (PMID: 31811016; NCT01677741). 31811016
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) 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 Advanced Solid Tumor predicted - sensitive BRAF Inhibitor Dabrafenib Phase I Actionable In a Phase I trial (BRF116013), Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in a median duration of treatment of 75.6 week in pediatric patients with BRAF V600-mutant advanced solid tumors, including low-grade (n=15) and high-grade (n=8) gliomas, Langerhans cell histiocytosis (n=2), neuroblastoma (n=1), and papillary thyroid cancer (n=1) (PMID: 31506385; NCT01677741). 31506385
BRAF V600X colorectal cancer no benefit RAF Inhibitor (Pan) 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 skin melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600X skin melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Guideline Actionable BRAF inhibitor plus MEK inhibitor combination therapy, such as Tafinlar (dabrafenib) plus Mekinist (trametinib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). 31566661 detail...
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) 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 skin melanoma sensitive BRAF Inhibitor Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in a partial response in 20% (8/41) of melanoma patients harboring BRAF V600 mutations, including V600E (33/41), V600K (5/41), and V600R (1/41) (PMID: 23414587; NCT01320085). 23414587
BRAF V600X melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Buparlisib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Buparlisib (BKM120) and Koselugo (selumetinib) 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 PIK3CA H1047X ovarian carcinoma predicted - sensitive Bevacizumab + Pegylated liposomal-doxorubicin + Temsirolimus Case Reports/Case Series Actionable In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in a patient with ovarian clear cell carcinoma harboring PIK3CA H1047 and BRAF V600 mutations (PMID: 21216929). 21216929
BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R melanoma predicted - resistant RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort Actionable In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). 24265153
BRAF V600X BRAF amp NRAS Q61K melanoma resistant RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort 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 V600X PTEN H93D melanoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Clinical Study - Cohort 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
BRAF V600X PTEN neg melanoma sensitive Uprosertib 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 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 lung non-small cell carcinoma sensitive BRAF Inhibitor 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 Advanced Solid Tumor sensitive BRAF Inhibitor 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 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 act mut Advanced Solid Tumor sensitive BRAF Inhibitor 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 lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
BRAF act mut melanoma no benefit RAF Inhibitor (Pan) 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 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 N581Y colon cancer resistant BRAF Inhibitor 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 amp lung non-small cell carcinoma not predictive unspecified immune checkpoint inhibitor Clinical Study Actionable In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). 31367539
BRAF V600E BRAF amp 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 V600E BRAF amp 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 Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification (PMID: 27312529). 27312529
BRAF V600E BRAF amp colorectal cancer resistant RAF Inhibitor (Pan) Cetuximab + Vemurafenib 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 V600E BRAF amp colorectal cancer resistant RAF Inhibitor (Pan) Cetuximab + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 16 weeks to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment, amplification of BRAF V600E was identified as an acquired alteration at the time of progression (PMID: 28951457). 28951457
BRAF V600E BRAF amp lung adenocarcinoma decreased response SCH772984 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived BRAF V600E mutant lung adenocarcinoma cells that acquired resistance to Erk inhibitor through BRAF amplification were less sensitive to SCH772984 in culture (PMID: 28714990). 28714990
BRAF V600E BRAF amp lung adenocarcinoma sensitive BRAF Inhibitor 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 V600E BRAF amp colorectal cancer predicted - resistant RAF Inhibitor (Pan) Panitumumab + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 24 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, amplification of BRAF V600E was identified as an acquired alteration at the time of progression (PMID: 28951457). 28951457
BRAF G469E melanoma sensitive RAF Inhibitor (Pan) Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment induced apoptosis and mitochondrial depolarization, and inhibited growth of melanoma cells harboring BRAF G469E in culture (PMID: 18794803). 18794803
BRAF G469E breast ductal carcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, only 1 patient with breast ductal carcinoma harboring BRAF G469E achieved a partial response with a tumor shrinkage of 50% at 4 months, but the patient died suddenly at 4.3 months with no disease progression (PMID: 31924734; NCT02465060). 31924734
BRAF G469E sarcomatoid carcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 6.9 months in a patient with spindle cell carcinoma harboring a BRAF G464E (PMID: 31924734; NCT02465060). 31924734
BRAF G469E melanoma resistant MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor U0126 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G469E demonstrated resistance to U0126 treatment in culture (PMID: 18794803). 18794803
BRAF D594N lung non-small cell 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 RAF Inhibitor (Pan) 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 D594N gallbladder cancer predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Case Reports/Case Series Actionable In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy resulted in stable disease in a patient with gallbladder cancer harboring BRAF D594N (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). detail...
BRAF D594N female reproductive organ cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecological cancer harboring BRAF D594N (PMID: 31924734; NCT02465060). 31924734
BRAF class 3 melanoma predicted - sensitive RAF Inhibitor (Pan) KIN-2787 Preclinical - Cell line xenograft Actionable In a preclinical study, KIN-2787 treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring a BRAF class 3 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). detail...
BRAF T599dup melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical study, a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in partial responses in 4 patients with metastatic melanoma harboring BRAF T599dup, with one patient also harboring CTNNB1 I35T (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination resulted in partial metabolic remission within six weeks in a patient with metastatic melanoma harboring BRAF T599dup (PMID: 29494756). 29494756
BRAF T599dup melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in regression of lymphadenopathy, lung nodules, and subcutaneous nodules in a patient with metastatic melanoma harboring BRAF T599dup, and at 9 months from treatment initiation, a partial response was still observed (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - resistant RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) resulted in disease progression in two patients with metastatic melanoma harboring BRAF T599dup (PMID: 35319964). 35319964
BRAF V600K colon cancer sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of colon cancer cells harboring BRAF V600K in culture (PMID: 30559419). 30559419
BRAF V600K melanoma predicted - sensitive Nivolumab Clinical Study - Cohort 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 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 skin melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic 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, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). detail... 27480103 detail...
BRAF V600K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved - On Companion Diagnostic 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 detail... detail...
BRAF V600K melanoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Pembrolizumab + Trametinib Phase II Actionable In a Phase II trial (IMPemBra), Keytruda (pembrolizumab) in combination with short-term or intermittent Tafinlar (dabrafenib) plus Mekinist (trametinib) resulted in improved median progression-free survival compared to Keytruda (pembrolizumab) monotherapy (27.0 vs 10.6 mo, p=0.13) in patients with treatment-naive advanced melanoma harboring BRAF V600E (n=26) or V600K (n=6) mutations (J Clin Oncol 38: 2020 (suppl; abstr 10021); NCT02625337). detail...
BRAF V600K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic 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) and both BRAF V600E and BRAF V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic 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). detail... 30219628 detail... detail...
BRAF V600K melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Pembrolizumab + Vemurafenib Phase I Actionable In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). detail...
BRAF V600K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib FDA approved - On Companion Diagnostic 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). detail... 25399551 detail...
BRAF V600K skin melanoma sensitive BRAF Inhibitor 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 cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). 30959471 detail...
BRAF V600K lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 2.1 and 6.8 months in the 2 patients harboring BRAF V600K (PMID: 31959346; NCT02304809). 31959346
BRAF V600K skin melanoma sensitive RAF Inhibitor (Pan) Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for cutaneous 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 skin melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 predicted - sensitive Pembrolizumab Clinical Study - Cohort 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 skin melanoma sensitive BRAF Inhibitor Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous 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 NRAS Q61K melanoma sensitive BRAF Inhibitor 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 BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib 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 NRAS Q61K melanoma resistant BRAF Inhibitor 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 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 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 MAP2K1 P124Q melanoma decreased response BRAF Inhibitor 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 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 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 P124L melanoma decreased response BRAF Inhibitor 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 MAP2K1 P124L melanoma predicted - resistant BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease progression within one month in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124L (PMID: 31980996). 31980996
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 P124S melanoma predicted - resistant BRAF Inhibitor Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in disease progression within 5 weeks in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124S (PMID: 24265153). 24265153
BRAF L485S BRAF V600E melanoma resistant BRAF Inhibitor Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, expression of BRAF L485S in melanoma cells harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). 31925410
BRAF G596D breast cancer predicted - resistant BRAF Inhibitor Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit Erk phosphorylation in breast cancer cells expressing BRAF G596D in culture (PMID: 31158244). 31158244
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic 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) and both BRAF V600E and V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Binimetinib + Encorafenib FDA approved - On Companion Diagnostic 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). detail... detail... detail... 30219628
BRAF V600E/K skin melanoma sensitive RAF Inhibitor (Pan) Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600E/K skin melanoma sensitive BRAF Inhibitor 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 cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). 30959471 detail...
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic 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, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). detail... detail... 27480103
BRAF V600E/K melanoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib + XL888 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 melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Phase II Actionable In a Phase II trial (S1320), intermittent dosing (3-week-off, 5-week-on) of Tafinlar (dabrafenib) and Mekinist (trametinib) did not improve median progression-free survival (5.5 v 9.0 months; HR=1.36, p=0.064, two-sided alpha=0.2) compared to continuous dosing in melanoma patients harboring BRAF V600E or V600K, and there were no significant differences in median overall survival, treatment response, or toxicity between the two treatment groups (PMID: 33020646; NCT02196181). 33020646
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib FDA approved - On Companion Diagnostic 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). detail... 28891408 detail...
BRAF V600E/K melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib FDA approved - On Companion Diagnostic 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). detail... detail... 25399551
BRAF V600E/K melanoma predicted - sensitive BRAF Inhibitor BGB-283 Case Reports/Case Series Actionable In a Phase I trial, Linfirafenib (BGB-283) treatment resulted in partial response in 15.1% (8/53) of solid tumor patients with BRAF mutations, including 5 of 23 patients with melanoma harboring BRAF V600E or V600K overall, and in the dose expansion phase 57.1% (4/7) patient with BRAF V600-mutant melanoma had a partial response (PMID: 32182156; NCT02610361). 32182156
BRAF V600E/K melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib FDA approved - On Companion Diagnostic 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 detail... detail...
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; NCT00687622). 22805292
BRAF V600E/K PIK3CA wild-type melanoma no benefit A66 Preclinical Actionable In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit TGX-221 Preclinical Actionable In a preclinical study, TGX-221 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive RAF Inhibitor (Pan) Vemurafenib + ZSTK474 Preclinical Actionable In a preclinical study, ZSTK474 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Selumetinib + Vemurafenib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive RAF Inhibitor (Pan) Dactolisib + Vemurafenib Preclinical Actionable In a preclinical study, BEZ235 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit Idelalisib Preclinical Actionable In a preclinical study, Zydelig (idelalisib) did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dactolisib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Koselugo (selumetinib) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib + ZSTK474 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and ZSTK474 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PTEN loss Advanced Solid Tumor predicted - sensitive RAF Inhibitor (Pan) PX-866 + Vemurafenib Phase I Actionable In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). 29051322
BRAF V600E/K CDKN2A loss RB1 pos melanoma predicted - sensitive RAF Inhibitor (Pan) Palbociclib + Vemurafenib Phase Ib/II Actionable In a phase I/II trial, Ibrance (palbociclib) plus Zelboraf (vemurafenib) was safe and resulted in an overall response rate (ORR) of 26.7% (4/15), disease control rate (DCR) of 80% (12/15), and progression-free survival (PFS) of 2.8 mo in metastatic melanoma patients with prior BRAF inhibitor treatment and BRAF V600E/K, CDKN2A loss, and RB1 expression, and an ORR of 27.8% (5/18), DCR of 83.3% (10/18) and 2.8 mo PFS when combined with pts without prior BRAF inhibitor treatment (PMID: 33947696; NCT02202200). 33947696
BRAF loss NRAS Q61K melanoma decreased response BRAF Inhibitor LXH 254 Preclinical - Cell culture Actionable In a preclinical study, CRISPR-Cas9 mediated knockout of BRAF in a melanoma cell line harboring NRAS Q61K led to decreased sensitivity to LXH254 treatment compared to parental cells harboring BRAF D287H and NRAS Q61K in culture (PMID: 33355204). 33355204
BRAF Y472C lung non-small cell 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 E451K breast cancer predicted - resistant BRAF Inhibitor Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) treatment resulted in increased Erk phosphorylation in breast cancer cells expressing BRAF E451K in culture (PMID: 31158244). 31158244
BRAF T599K breast cancer predicted - resistant BRAF Inhibitor Dabrafenib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit Erk phosphorylation in breast cancer cells expressing BRAF T599K in culture (PMID: 31158244). 31158244
BRAF L597V lung adenocarcinoma resistant Ulixertinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ulixertinib (BVD-523) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant BRAF Inhibitor Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Tafinlar (dabrafenib) in culture (PMID: 32540409). 32540409
BRAF L597V endometrial adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 7.9 months in a patient with endometrial adenocarcinoma harboring BRAF L597V (PMID: 31924734; NCT02465060). 31924734
BRAF L597V lung adenocarcinoma resistant MK-8353 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with MK-8353 in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant RAF Inhibitor (Pan) MLN2480 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with MLN2480 (TAK-580) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma sensitive BRAF Inhibitor LXH 254 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant BRAF Inhibitor Encorafenib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Braftovi (encorafenib) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma sensitive BRAF Inhibitor BGB-283 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with Lifirafenib (BGB-283) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant LY3214996 Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with LY3214996 in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant Ravoxertinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF L597V Advanced Solid Tumor resistant RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF L597V (PMID: 26343582). 26343582
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response BRAF Inhibitor PLX7904 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response BRAF Inhibitor Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma sensitive RAF Inhibitor (Pan) AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma sensitive RAF Inhibitor (Pan) TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). 27523909
BRAF L597V NRAS Q61K lung non-small cell carcinoma decreased response RAF Inhibitor (Pan) Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). 27523909
BRAF G466A lung adenocarcinoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 1 and stable disease in 2 patients with lung adenocarcinoma harboring BRAF G466A (PMID: 31924734; NCT02465060). 31924734
BRAF G466A prostate cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). 31924734
BRAF G466A lung non-small cell carcinoma predicted - sensitive BRAF Inhibitor LTT462 + LXH 254 Case Reports/Case Series Actionable In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF G466A achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). detail...
BRAF G466A gastrointestinal system cancer no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gastrointestinal system cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). 31924734
BRAF G466A lung non-small cell carcinoma no benefit RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G466A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
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 melanoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment inhibited growth of skin and lung nodules by 30% and resulted in a duration of response of over 4 months in a melanoma patient harboring BRAF L597R, and inhibited Erk activation and reduced viability of melanoma cells derived from the patient in culture (PMID: 23715574). 23715574
BRAF L597R prostate cancer sensitive BRAF Inhibitor PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of prostate cancer cells harboring BRAF L597R in culture (PMID: 30559419). 30559419
BRAF L597R melanoma predicted - sensitive BRAF Inhibitor Dabrafenib Preclinical - Patient cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment inhibited Erk activation and reduced viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). 23715574
BRAF L597R lung adenocarcinoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring BRAF L597R demonstrated clinical improvement and a tumor response at 13 weeks with resolution of hepatic metastasis and mediastinal lymphadenopathy when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and at the 12 month follow up remained on treatment, showing no disease progression (PMID: 32540409). 32540409
BRAF L597R Advanced Solid Tumor sensitive RAF Inhibitor (Pan) 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 L597R melanoma predicted - sensitive RAF Inhibitor (Pan) Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). 23715574
BRAF V600D melanoma sensitive RAF Inhibitor (Pan) 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 melanoma sensitive BRAF Inhibitor 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 RAF Inhibitor (Pan) 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 ASTX029 Preclinical - Cell culture Actionable In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring BRAF V600D in culture (PMID: 34330842). 34330842
BRAF V600D pilocytic astrocytoma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Dabrafenib + Trametinib Case Reports/Case Series 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 RAF Inhibitor (Pan) 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 BRAF Inhibitor 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 lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 3.8 months in the patient harboring BRAF V600D (PMID: 31959346; NCT02304809). 31959346
BRAF V600D melanoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Belvarafenib + Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in a melanoma cell line harboring BRAF V600D resulted in greater inhibition of cell proliferation in culture compared to single agent alone (PMID: 33953400). 33953400
BRAF V600D melanoma sensitive RAF Inhibitor (Pan) 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 RAF Inhibitor (Pan) 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 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 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 V600M lung non-small cell carcinoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 5.9 months in the patient harboring BRAF V600M (PMID: 31959346; NCT02304809). 31959346
BRAF V600E BRAF V600M melanoma predicted - sensitive BRAF Inhibitor Dabrafenib Case Reports/Case Series Actionable In a clinical case study, a patient with rapidly growing malignant melanoma harboring BRAF V600E and V600M achieved a 60% reduction in tumor size 1 week following treatment with Tafinlar (dabrafenib), and the tumor completely disappeared 1 month after beginning treatment (PMID: 23031422). 23031422
BRAF G464E Advanced Solid Tumor resistant RAF Inhibitor (Pan) 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 V600E ovarian cancer predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series 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 ovarian cancer predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Phase II Actionable In a Phase II trial (VE-BASKET), responses were seen in ovarian cancer patients harboring BRAF V600E (n=4) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). 32029534
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 MEK1 Inhibitor E6201 Case Reports/Case Series Actionable In a Phase I trial, a patient with metastatic melanoma and brain metastasis harboring BRAF V600E demonstrated an ongoing near complete response with an overall survival of more than 8 years, and preclinical analysis of melanoma cell lines harboring homozygous or heterozygous BRAF V600E in culture were sensitive to treatment with E6201 (PMID: 30264293). 30264293
BRAF V600E anaplastic oligodendroglioma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). detail...
BRAF V600E pilocytic astrocytoma predicted - sensitive RAF Inhibitor (Pan) Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with pilocytic astrrocytoma harboring BRAF V600E who stayed on treatment for 15.3 months (PMID: 30351999; NCT01524978). 30351999
BRAF V600E colorectal cancer sensitive ERAS-007 Preclinical - Pdx & cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited cell proliferation and Erk signaling in colorectal cancer cell lines harboring BRAF V600E in culture, and induced tumor regression in two patient-derived xenograft (PDX) models (PMID: 34337566). 34337566
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 low grade glioma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive RAF Inhibitor (Pan) TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive RAF Inhibitor (Pan) 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 melanoma sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PLX4720 + Selumetinib 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 skin melanoma no benefit MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Trametinib + YM-254890 Preclinical - Cell culture Actionable In a preclinical study, combination treatment with YM-254890 and Mekinist (trametinib) did not result in synergistic inhibition of cell viability of a cutaneous melanoma cell line harboring BRAF V600E in culture (PMID: 33229459). 33229459
BRAF V600E thyroid gland follicular carcinoma sensitive BRAF Inhibitor Dabrafenib Guideline Actionable Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid follicular carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). detail...
BRAF V600E colon cancer sensitive BRAF Inhibitor Cetuximab + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). detail...
BRAF V600E childhood pilocytic astrocytoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Selumetinib Phase I Actionable In a Phase I trial, Koselugo (selumetinib) treatment resulted in a sustained partial response (PR) in 36% (9/25) and stable disease in 36% (9/25) of pediatric patients with pilocytic astrocytoma harboring KIAA1549-BRAF (n=18) or BRAF V600E (n=7), with a 2-year progression-free survival of 70%, and 29% (2/7) of the patients harboring BRAF V600E achieved PR (PMID: 31151904; NCT01089101). 31151904
BRAF V600E high grade glioma predicted - sensitive BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor PLX4720 + Selumetinib 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 pilocytic astrocytoma predicted - sensitive BRAF Inhibitor Dabrafenib Case Reports/Case Series 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 melanoma predicted - resistant KRT-232 Preclinical - Pdx Actionable In a preclinical study, patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E demonstrated resistance to treatment with KRT-232 (AMG 232) (PMID: 32234759). 32234759
BRAF V600E hairy cell leukemia sensitive RAF Inhibitor (Pan) 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 melanoma sensitive RAF Inhibitor (Pan) Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in an overall response rate of 81% (26/32; 2 complete responses, 24 partial responses), and inhibition of tumor Erk and Ccnd1, and reduced cell proliferation in metastatic melanoma patients harboring BRAF V600E (PMID: 20818844; NCT00215605). 20818844
BRAF V600E melanoma sensitive RAF Inhibitor (Pan) Vemurafenib FDA approved - On Companion Diagnostic 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, PMID: 21639808; NCT01006980), and BRAF V600E is included on the companion diagnostic (FDA.gov). 28961848 detail... detail... 21639808
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 anaplastic astrocytoma sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). detail...
BRAF V600E glioblastoma decreased response BRAF Inhibitor 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 melanoma predicted - resistant BI-3406 Preclinical - Cell line xenograft Actionable In a preclinical study, BI-3406 treatment failed to inhibit growth of KRAS wild-type melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 32816843). 32816843
BRAF V600E endometrial adenocarcinoma predicted - sensitive BRAF Inhibitor Dabrafenib + Rabeprazole + Rifampin Case Reports/Case Series Actionable In a Phase I trial, combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, that recurred 11 years after original diagnosis and was refractory to treatment with chemotherapy, led to reduction of lung metastases and pelvic tissue mass at three months, but a slight increase in pelvic mass was observed at six months (PMID: 33537843; NCT01954043). 33537843
BRAF V600E pancreatic ductal adenocarcinoma predicted - sensitive MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor Cobimetinib + Gemcitabine + Nab-paclitaxel Case Reports/Case Series Actionable In a clinical case study, Gemzar (gemcitabine), Abraxane (nab-paclitaxel), and Cotellic (cobimetinib) combination treatment resulted in a complete radiologic response within 6 months of initiation lasting at least 16 months in a patient with microsatellite stable, KRAS wild-type pancreatic ductal adenocarcinoma harboring BRAF V600E (PMID: 34667063). 34667063
BRAF V600E rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org).