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| Profile Name | BRAF D287H |
| Gene Variant Detail | |
| Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF class 3 | melanoma | predicted - sensitive | 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 G534D NRAS Q61L | melanoma | resistant | 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 D594G | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | ampulla of Vater cancer | predicted - sensitive | 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 NRAS G12D | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | sensitive | 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 D594G NRAS G12D | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF V47_D380del | melanoma | predicted - resistant | 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 | colorectal cancer | predicted - resistant | 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 V47_D380del BRAF V600E | melanoma | resistant | 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 R239Q BRAF L597S | melanoma | sensitive | 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 | 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 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 | 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 V600R | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | 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 | 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 | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | Dabrafenib | 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 | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX7904 inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF L485Y | lung non-small cell carcinoma | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring BRAF L485Y were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). | 19276360 | |
| BRAF G596D | breast cancer | predicted - resistant | 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 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 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 I463W BRAF V600E | melanoma | resistant | 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 L597Q | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF L597Q (PMID: 26343582). | 26343582 | |
| BRAF L597Q | Advanced Solid Tumor | resistant | 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 | 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 | 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 | 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 | 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 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 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 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 L505H | melanoma | resistant | 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 | 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 loss NRAS Q61K | melanoma | decreased response | 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 T529M BRAF V600E | Advanced Solid Tumor | predicted - sensitive | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF T529M BRAF V600E | Advanced Solid Tumor | predicted - resistant | SB590885 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). | 20538618 | |
| BRAF T529M BRAF V600E | Advanced Solid Tumor | predicted - resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). | 20538618 | |
| BRAF 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 - sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF V600E/K | melanoma | sensitive | 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 | 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 | 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 | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | skin melanoma | sensitive | 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 | melanoma | predicted - sensitive | 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 | 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 | melanoma | sensitive | 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 | predicted - sensitive | 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 | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). | 30959471 detail... |
| 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 | 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 | no benefit | A66 | Preclinical | Actionable | In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). | 26137449 | |
| BRAF V600E/K PIK3CA wild-type | melanoma | sensitive | 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 | 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 | 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 PIK3CA wild-type | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 PTEN loss | Advanced Solid Tumor | predicted - sensitive | PX-866 + Vemurafenib | Phase I | Actionable | In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). | 29051322 | |
| BRAF V600E/K CDKN2A loss RB1 pos | melanoma | predicted - sensitive | 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 K601N | chronic lymphocytic leukemia | sensitive | 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 | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601N (PMID: 26343582). | 26343582 | |
| BRAF K601N | hematologic cancer | sensitive | 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 | lung non-small cell carcinoma | no benefit | 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 | 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 G469A BRAF W604C | lung adenocarcinoma | predicted - sensitive | 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 D287H NRAS Q61K | melanoma | predicted - sensitive | 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 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 T529I BRAF V600E | Advanced Solid Tumor | predicted - resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - resistant | SB590885 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - sensitive | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF 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 G596V | lung non-small cell carcinoma | predicted - sensitive | 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 | 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 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 F247L | Advanced Solid Tumor | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Tafinlar (dabrafenib) in culture (PMID: 28512244). | 28512244 | |
| BRAF 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 | 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 | 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 | 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 | 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 | 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 | 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 | melanoma | predicted - sensitive | 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 | 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 | Advanced Solid Tumor | resistant | 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 | 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 | 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 | resistant | 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 | 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 | 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 | 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 | melanoma | predicted - sensitive | RAF265 | Phase I | Actionable | In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). | 28719152 | |
| BRAF wild-type | melanoma | predicted - sensitive | 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 | no benefit | 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 | 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 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 | 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 | 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 | sensitive | 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 | 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 | 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 wild-type | melanoma | resistant | 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 Q61K | melanoma | resistant | 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 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 non-small cell carcinoma | no benefit | 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 | 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 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 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 G464R | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464R (PMID: 26343582). | 26343582 | |
| BRAF T599dup | melanoma | predicted - sensitive | 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 | 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 | 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 | 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 E451K | breast cancer | predicted - resistant | 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 N486_P490del BRAF R509H | Advanced Solid Tumor | sensitive | 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 | 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 | resistant | 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 N486_P490del BRAF R509H BRAF V600E | Advanced Solid Tumor | sensitive | 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 R509H BRAF V600E | Advanced Solid Tumor | sensitive | 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 R509H BRAF V600E | Advanced Solid Tumor | sensitive | 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 G464E | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464E (PMID: 26343582). | 26343582 | |
| BRAF G464E | 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 V600K | skin melanoma | sensitive | 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 | sensitive | 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 | 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 | 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 | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | colon cancer | sensitive | 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 | skin melanoma | sensitive | 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 | 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 | 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 | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | lung non-small cell carcinoma | predicted - sensitive | 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 | 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 | melanoma | sensitive | 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 | 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 | predicted - sensitive | 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 NRAS Q61K | melanoma | sensitive | 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 | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | 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 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 P124Q | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 |
| BRAF V600K MAP2K1 P124L | melanoma | 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 | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | predicted - resistant | 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 P124S | melanoma | predicted - resistant | 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 V600L | mucosal melanoma | predicted - sensitive | 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 G469A BRAF L584P | melanoma | predicted - sensitive | 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 V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). | 33568355 |
| BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) and Mekinist (trametinib) combination treatment resulted in decreased tumor markers in a patient with pancreatic ductal adenocarcinoma harboring BRAF V600E, as well as a germline ATM mutation, and the patient received 13 months of combination therapy and was followed for 24 months (PMID: 35145907). | 35145907 |
| BRAF V600E | colorectal cancer | sensitive | SCH772984 | Preclinical | Actionable | In a preclinical study, SCH772984 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E | thyroid gland cancer | sensitive | Dasatinib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 | |
| BRAF V600E | thyroid gland papillary carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a papillary thyroid carcinoma patient who progressed on Lenvima (lenvatinib) was found to harbor BRAF V600E and was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) on a clinical trial, resulting in partial response in the thyroid bed, cervical and intrathoracic lymph nodes, and pulmonary lesions, with a decrease in target lesion size of 67%, and the patient remained on treatment for 18 months before stopping due to progression (PMID: 31085763). | 31085763 |
| BRAF V600E | colorectal cancer | resistant | SHP099 | Preclinical - Cell culture | Actionable | In a preclincial study, colorectal cancer cell lines harboring BRAF V600E demonstrated resistance to SHP099 in culture (PMID: 27362227). | 27362227 | |
| BRAF V600E | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Clinical Study - Cohort | Actionable | In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including BRAF V600E, activating KRAS, HRAS, or NRAS mutations, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620). | detail... |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | melanoma | sensitive | S3I-201 | Preclinical | Actionable | In a preclinical study, S3I-201 inhibited cell invasion and Stat3 signaling in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). | 23242808 | |
| BRAF V600E | 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 | lung non-small cell carcinoma | predicted - sensitive | 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 V600E achieving an unconfirmed PR and 1 achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... | |
| BRAF V600E | high grade glioma | predicted - sensitive | Vemurafenib + ZM336372 | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Zelboraf (vemurafenib) and ZM336372 treatment led to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | colorectal cancer | decreased response | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, treatment with Keytruda (pembrolizumab), Opdivo (nivolumab), or combination treatment with Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with mismatch repair-deficient colorectal cancer harboring BRAF V600E vs. patients with wild-type BRAF resulted in a lower objective response rate (44.4% vs. 74.2%, p = 0.12) and shorter progression-free survival (PFS) rates (1-year PFS 40% vs. 73.3%, 2-year PFS 26.7% vs. 73.3%) (PMID: 33631043). | 33631043 | |
| BRAF V600E | colon carcinoma | sensitive | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human colon carcinoma cell line (PMID: 22319199). | 22319199 | |
| BRAF V600E | melanoma | sensitive | KRT-232 + Navitoclax | Preclinical - Pdx | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Navitoclax (ABT-263) resulted in a greater response than either drug alone in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E, leading to tumor regression (PMID: 32234759). | 32234759 | |
| BRAF V600E | colorectal cancer | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). | 24885690 | |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a complete intracranial response 2 months after treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, although the disease progressed 1 month later (PMID: 31386052). | 31386052 | |
| BRAF V600E | pleomorphic xanthoastrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 42.9% (3/7, 1 complete response, 2 partial responses) and a clinical benefit rate of 57% in patients with pleomorphic xanthoastrocytoma harboring BRAF V600E, with a median progression-free survival of 5.7 months, and median overall survival not reached (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colorectal cancer | sensitive | Panitumumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 25589621). | 25589621 | |
| BRAF V600E | melanoma | sensitive | AZD0364 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD0364 (ATG-017) inhibited cell growth, decreased phosphorylation of Erk target genes, and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E in culture, and resulted in tumor regression in cell line xenograft models (PMID: 33273059). | 33273059 | |
| BRAF V600E | colon cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | endometrial adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Rabeprazole + Rifampin + Trametinib | Case Reports/Case Series | Actionable | In a Phase I trial, the addition of Mekinist (trametinib) to the combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin resulted in a maintained radiographic response of lung metastases and stable pelvic mass size in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, which lasted for 12 months (PMID: 33537843; NCT01954043). | 33537843 |
| BRAF V600E | thyroid gland cancer | sensitive | PLX4720 + Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Iclusig (ponatinib) and PLX4720 treatment demonstrated synergy, and inhibited Erk, Mek, and c-jun phosphorylation, reduced cell proliferation, colony formation, and migration, and induced apoptosis in thyroid cancer cells harboring BRAF V600E and in PLX4720-resistant cells harboring BRAF V600E in culture, and inhibited tumor growth, reduced lung and liver metastases, and increased survival in cell line xenograft models (PMID: 31937621). | 31937621 | |
| BRAF V600E | colorectal cancer | sensitive | CCT196969 | Preclinical - Cell culture | Actionable | In a preclinical study, CCT196969 inhibited growth of BRAF-mutant colorectal cancer cell lines in culture (PMID: 25500121), which have been reported to harbor BRAF V600E (PMID: 15294323). | 25500121 15294323 | |
| BRAF V600E | melanoma | sensitive | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | Dabrafenib + JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and JSI-1187 led to synergistic inhibition of tumor growth in a colorectal cancer cell line xenograft model harboring BRAF V600E (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | colon cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). | 16273091 |
| BRAF V600E | ganglioglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PAC-1 + Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PAC-1 to Mekinist (trametinib) and Zelboraf (vemurafenib) led to greater levels of caspase-3 activity and apoptosis in melanoma cells harboring BRAF V600E when compared to Zelboraf (vemurafenib) and Mekinist (trametinib) treatment without PAC-1 (PMID: 27297867). | 27297867 |
| BRAF V600E | rectum cancer | resistant | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | colorectal cancer | sensitive | Encorafenib | Phase I | Actionable | In a Phase I trial, Encorafenib (LGX818) showed activity in patients with advanced metastatic colorectal cancer harboring a BRAF V600E mutation, resulting in a median progression-free survival of 4 months and a best response of stable disease in 66.7% (12/18) (Ann Oncol (2014) 25 (suppl 4): iv182-iv183). | detail... | |
| BRAF V600E | endometrial adenocarcinoma | predicted - sensitive | 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 | melanoma | sensitive | DETD-35 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). | 27048951 | |
| BRAF V600E | colorectal cancer | sensitive | INU-152 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INU-152 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture, and reduced tumor growth in BRAF V600E-mutant colorectal cancer cell line xenograft models (PMID: 28645859). | 28645859 | |
| BRAF V600E | 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 V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). | 30268448 | |
| BRAF V600E | melanoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | colorectal cancer | sensitive | Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | melanoma | sensitive | 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 | colorectal cancer | sensitive | Gefitinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Iressa (gefitinib) decreased the number of viable colorectal cancer cells harboring a BRAF V600E mutation in cell culture (PMID: 22448344). | 22448344 | |
| BRAF V600E | anaplastic oligodendroglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| BRAF V600E | thyroid gland Hurthle cell carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid Hurthle cell carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | 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 V600E | melanoma | sensitive | 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 | hairy cell leukemia | predicted - sensitive | Ruxolitinib + Vemurafenib | Phase II | Actionable | In a Phase II trial (HCL-PG03), combined Zelboraf (vemurafenib) and Jakafi (ruxolitinib) therapy in relapsed or refractory hairy cell leukemia patients with BRAF V600E demonstrated safety, and led to complete response (CR) in 87% (26/30) of patients, including 17 (65%) with negative minimal residual disease, a progression-free survival rate of 78% at a median follow-up of 37 months, and a relapse-free survival rate of 85% in the 26 patients with a CR at a median follow-up of 34 months (PMID: 33979489). | 33979489 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | neuroendocrine carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with neuroendocrine carcinoma harboring BRAF V600E (n=3) when treated with Zelboraf (vemurafenib), including 1 patient with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | melanoma | sensitive | Dabrafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III clinical trial (BREAK-3) that supported FDA approval, Tafinlar (dabrafenib) improved median progression-free survival compared to Deticene (dacarbazine) (5.1 vs 2.7 months, HR=0.3, p<0.0001) in patients with BRAF V600E positive melanoma (PMID: 22735384; NCT01227889). | detail... detail... 22735384 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Phase I | Actionable | In a Phase I trial, Cotellic (cobimetinib) treatment resulted in a confirmed partial response in six melanoma patients harboring BRAF V600E (PMID: 27424159). | 27424159 |
| BRAF V600E | glioblastoma | sensitive | BI2536 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). | 26573800 | |
| BRAF V600E | Erdheim-Chester disease | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CI-1040 inhibited growth of a human ovarian cancer cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 19018267). | 19018267 |
| BRAF V600E | breast cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (TAPUR), Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy resulted in a complete response lasting 108.9 weeks in a patient with advanced breast cancer harboring BRAF V600E (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3008; NCT02693535). | detail... |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | melanoma | sensitive | SBI-0640756 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) in combination with SBI-0640756 inhibited the association of eIF4G1 and eIF4E in Zelboraf (vemurafenib) resistant human melanoma cell lines harboring BRAF V600E in culture and reduced tumor growth in xenograft models (PMID: 26603897). | 26603897 | |
| BRAF V600E | melanoma | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF709 inhibited Erk signaling and proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 29343524). | 29343524 | |
| BRAF V600E | colorectal cancer | sensitive | Afatinib + BI 882370 | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Gilotrif (afatinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 | |
| BRAF V600E | ovarian cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (TAPUR), Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy resulted in a complete response lasting 5.1 weeks in a patient with advanced ovarian cancer harboring BRAF V600E (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3008; NCT02693535). | detail... |
| BRAF V600E | high grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 33% (15/45, 3 complete responses, 12 partial responses) in patients with high-grade glioma harboring BRAF V600E, with a median duration of response of 36.9 months, a median progression-free survival of 3.8 months, and an overall survival of 17.6 months (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | melanoma | sensitive | 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 | high grade glioma | predicted - sensitive | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cediranib + PLX4720 + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, PLX4720, Cediranib (AZD-2171) and Koselugo (selumetinib) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Dabrafenib | Clinical Study - Cohort | Actionable | In a clinical study, Tafinlar (dabrafenib) treatment stimulated radioiodine uptake in 60% (6/10) of patients with metastatic iodine-refractory papillary thyroid cancer harboring BRAF V600E (PMID: 25549723; NCT01534897). | 25549723 | |
| BRAF V600E | basal cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in stable disease after three months of treatment in a patient with basal cell carcinoma harboring BRAF V600E (PMID: 33537843) | 33537843 |
| BRAF V600E | colorectal cancer | sensitive | PLX4720 + TAK-632 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and TAK-632 combination treatment resulted in durable inhibition of Erk signaling and tumor growth in xenograft models of colorectal cancer cells harboring BRAF V600E (PMID: 27523909). | 27523909 | |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in a complete or partial response in three papillary thyroid carcinoma patients harboring BRAF V600E, with one patient having a response that lasted for 8 months who remained progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844; NCT00215605). | 20818844 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a partial response in 38.5% (10/26) of patients with metastatic or unresectable, radioactive iodine-refractory papillary thyroid carcinoma harboring BRAF V600E that were multikinase inhibitor-naive, with a disease control rate of 73%, and a median progression-free survival of 18.2 months (PMID: 27460442; NCT01286753). | 27460442 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | thyroid gland follicular carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) 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 | melanoma | sensitive | 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 | 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 | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 V600E | ovarian serous 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 5 patients with low grade serous ovarian carcinoma, 4 achieved a partial response (PR), 1 had stable disease, 3 of the PRs lasted over 12 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | high grade glioma | predicted - sensitive | Everolimus + PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 | |
| BRAF V600E | melanoma | no benefit | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with Ibrance (palbociclib) in a melanoma cell line xenograft model harboring BRAF V600E resulted in no benefit, demonstrating low but continuous growth (PMID: 27488531). | 27488531 | |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | BGB-283 | Case Reports/Case Series | 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 1 patient with BRAF V600E-mutant low-grade serous ovarian cancer (PMID: 32182156; NCT02610361). | 32182156 | |
| BRAF V600E | glioblastoma | decreased response | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). | 26573800 | |
| BRAF V600E | melanoma | no benefit | Sorafenib | Phase II | Actionable | In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203). | 22394203 16880785 | |
| BRAF V600E | colorectal cancer | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640756 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | 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 clinical benefit that lasted for more than 14 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). | 29632053 |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | C6-ceramide nanoliposome + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Nexavar (sorafenib) treatment in combination with C6-ceramide nanoliposome inhibited Mek and Akt phosphorylation, led to enhanced apoptosis and inhibition of proliferation, and synergistically reduced viability of melanoma cells harboring BRAF V600E in culture, and enhanced inhibition of tumor growth in a cell line xenograft model (PMID: 18519791). | 18519791 | |
| BRAF V600E | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 |
| BRAF V600E | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). | 24422853 | |
| BRAF V600E | melanoma | predicted - sensitive | RAF265 | Phase I | Actionable | In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). | 28719152 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) inhibited tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 28649441). | 28649441 |
| BRAF V600E | Advanced Solid Tumor | sensitive | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited Erk phosphorylation and cell proliferation in BRAF V600E expressing cells in culture (PMID: 20538618). | 20538618 | |
| BRAF V600E | colorectal cancer | sensitive | Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in colorectal cancer cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). | 28939558 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, JSI-1187 treatment in a colorectal cancer cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor regression and dose-dependent tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | diffuse large B-cell lymphoma | sensitive | ERAS-007 | Preclinical - Cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of diffuse large B-cell lymphoma cells harboring BRAF V600E in culture (PMID: 34337566). | 34337566 | |
| BRAF V600E | melanoma | sensitive | Navitoclax + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and navitoclax (ABT-263) worked synergistically to inhibit growth and increase apoptosis of BRAF V600E mutant melanoma cells in culture and in xenografts (PMID: 24983357). | 24983357 | |
| BRAF V600E | IDH-wildtype glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in disease stability over 15 months in a patient with epithelioid glioblastoma harboring BRAF V600E, who previously progressed on conventional treatment options (PMID: 34232949). | 34232949 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | Ravoxertinib | Case Reports/Case Series | Actionable | In a Phase I trial, two colorectal cancer patients harboring BRAF V600E achieved partial responses lasting 21 and 73 weeks following treatment with Ravoxertinib (GDC-0994) (PMID: 31848189; NCT01875705). | 31848189 | |
| BRAF V600E | hairy cell leukemia | sensitive | Vemurafenib | Phase II | Actionable | In two Phase II clinical studies, patients with refractory hairy cell leukemia harboring BRAF V600E responded to Zelboraf (vemurafenib) with overall response rates of 96% (25/26) and 100% (24/24) as well as complete response rates of 35% (9/26) and 42% (10/24) with median follow up times of 8 and 12 weeks, respectively (PMID: 26352686). | 26352686 | |
| BRAF V600E | histiocytic and dendritic cell cancer | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with histiocytic neoplasms harboring BRAF V600E (n=27) when treated with Zelboraf (vemurafenib), including 15 patients with a partial response and 2 patients with a complete response (PMID: 32029534; NCT01524978). | 32029534 | |
| 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 | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for metastatic thyroid gland anaplastic carcinoma patients harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with advanced or metastatic thyroid gland anaplastic carcinoma harboring BRAF V600E (PMID: 31549998, PMID: 35491008; ESMO.org). | 31549998 detail... 35491008 |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Clinical Study | Actionable | In a clinical case report, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). | 27697975 |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 61% (20/33; 3 complete responses, 17 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E, with 12-month duration of response rate of 50%, a median progression-free survival and overall survival of 6.7 and 14.5 months, respectively (PMID: 35026411; NCT02034110). | 35026411 detail... detail... detail... |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, RO4987655 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). | 26438159 |
| BRAF V600E | melanoma | sensitive | ASN003 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma xenograft model harboring BRAF V600E demonstrated tumor regression when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). | detail... | |
| BRAF V600E | cholangiocarcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with cholangiocarcinoma harboring BRAF V600E (n=9) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with BRAF V600E positive advanced solid tumors other than melanoma, thyroid cancer, or colorectal cancer, with a median duration of response of 25.1 months, and a disease control rate of 75.9% (22/29) (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | Erdheim-Chester disease | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for cutaneous melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600E, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). | detail... |
| BRAF V600E | high grade glioma | no benefit | ZM336372 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ZM336372 treatment did not lead to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical | Actionable | In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
| BRAF V600E | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | ASTX029 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with ASTX029 and Zelboraf (vemurafenib) resulted in decreased viability of melanoma cells harboring BRAF V600E compared to either agent alone in culture (PMID: 34330842). | 34330842 | |
| BRAF V600E | melanoma | sensitive | Encorafenib | Preclinical - Cell line xenograft | Actionable | In preclinical studies, Encorafenib (LGX818) treatment of human melanoma xenograft models with BRAF V600E significantly decreased Mek activation and resulted in tumor regression (Cancer Res: 72(8) Suppl 1, Abstract #3790). | detail... | |
| BRAF V600E | melanoma | sensitive | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring monomeric BRAF V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | melanoma | sensitive | BGB-283 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in melanoma cell lines harboring BRAF V600E in culture (PMID: 26208524). | 26208524 | |
| BRAF V600E | melanoma | no benefit | SHP099 | Preclinical | Actionable | In a preclinical study, SHP099 did not inhibit proliferation or ERK activation in a melanoma cell line harboring BRAF V600E in culture (PMID: 27362227). | 27362227 | |
| BRAF V600E | thyroid gland anaplastic carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a response in patients with anaplastic thyroid carcinoma harboring BRAF V600E (n=12), including 1 patient with a complete response and 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | lung papillary adenocarcinoma | predicted - sensitive | 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 regression of the lesions in the chest, abdomen and brain in a patient with lung papillary carcinoma harboring BRAF V600E but progression was observed 3 months later (PMID: 34178685). | 34178685 |
| BRAF V600E | colorectal cancer | sensitive | Alpelisib + Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | skin melanoma | sensitive | Ganetespib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Hsp90 inhibitor Ganetespib destabilized BRAF, especially BRAF V600E, resulted in loss of cell viability in culture and antitumor effects in cell line xenograft models of melanoma (PMID: 24398428). | 24398428 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + TW-37 | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colorectal cancer | sensitive | Dabrafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation had increased sensitivity to Tafinlar (dabrafenib) in culture compared to cell lines with wild-type BRAF (PMID: 24885690). | 24885690 | |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | 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 | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) decreased tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 23942066). | 23942066 |
| BRAF V600E | hairy cell leukemia | not applicable | N/A | Guideline | Diagnostic | BRAF V600E is diagnostic and aids in distinguishing classic hairy cell leukemia (cHCL) from variant hairy cell leukemia (HCLv) and other B-cell lymphomas and leukemias (PMID: 29118233, NCCN.org). | detail... 29118233 | |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture, and suppressed tumor growth in patient-derived xenograft (PDX) models (PMID: 33568355). | 33568355 |
| 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 | colon adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a patient with colon adenocarcinoma harboring BRAF V600E led to stable disease, and treatment continued for eight months, at which time some disease progression was observed (PMID: 33568355). | 33568355 |
| BRAF V600E | biliary tract cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) in combination with Mekinist (trametinib) demonstrated a manageable safety profile and resulted in an overall response rate of 51% (22/43, all partial responses) in patients with biliary tract cancer harboring BRAF V600E, with a median duration of response of 9 months, a median progression-free survival of 9 months, and a median overall survival of 14 months (PMID: 32818466; NCT02034110). | 32818466 |
| BRAF V600E | biliary tract cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | Regorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). | 21170960 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (BEACON CRC) trial that supported FDA approval, Braftovi (encorafenib) and Erbitux (cetuximab) combination treatment (n=113) resulted in improved median overall survival (8.4 vs 5.4 months, HR=0.60, p<0.001), confirmed response rate (20% vs 2%, p<0.001), and median progression-free survival (4.2 vs 1.5 months, HR=0.40, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). | detail... 31566309 | |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response 1 week after treatment in a patient with epithelioid type glioblastoma harboring BRAF V600E, although the patient soon passed due to complications (PMID: 31386052). | 31386052 | |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in tumor regression as confirmed by MRI after 3-weeks of treatment in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 31217909). | 31217909 | |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in stable disease as best response in 3 of 6 patients with glioblastoma harboring BRAF V600E, with stable disease lasting 3.6, 3.7, and 12.9 months, respectively (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment in a colorectal cancer patient harboring BRAF V600E led to a tumor reduction of 39% after 8 weeks of treatment and a confirmed partial response at 12 weeks, and response to treatment was maintained for 8 weeks (PMID: 33953400; NCT03118817). | 33953400 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF V600E (PMID: 30833748). | 30833748 |
| BRAF V600E | intrahepatic cholangiocarcinoma | 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with intrahepatic cholangiocarcinoma, 3 achieved a partial response, with individual progression-free survival of 12.8, 9.1, and 29.4 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib) led to a partial response after 1 month of treatment in a microsatellite stable pancreatic ductal adenocarcinoma patient with BRAF V600E and amplification of FGFR1 and NOTCH2, with significant decrease in hepatic metastatic lesions and undetectable lung lesions at 6 months, and a progression-free survival of at least 6 months (PMID: 35382161). | 35382161 |
| BRAF V600E | colon cancer | predicted - sensitive | Cetuximab + Sorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF V600E demonstrated mixed radiographic response with slight progression in some locations and stable disease in other locations for 7 months following treatment with the combination of Nexavar (sorafenib) and Erbitux (cetuximab) (PMID: 23792568). | 23792568 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cell lines harboring BRAF V600E demonstrated decreased response to Zelboraf (vemurafenib) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) did not demonstrate meaningful clinical activity as a single agent, resulted in partial response in 5% (1/21) and stable disease in 33% (7/21) of patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 26460303; NCT00405587). | 26460303 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). | 22281684 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | glioblastoma | sensitive | BI2536 + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). | 26573800 | |
| BRAF V600E | melanoma | sensitive | Saracatinib | Preclinical | Actionable | In a preclinical study, saracatinib inhibited proliferation of human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). | 23242808 | |
| BRAF V600E | thyroid gland cancer | sensitive | Lapatinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, the combination of Tykerb (lapatinib) and Zelboraf (vemurafenib) inhibited growth of thyroid cancer cells harboring a BRAF V600E mutation in culture and in BRAF-mutant mouse models of thyroid cancer (PMID: 23365119). | 23365119 | |
| BRAF V600E | ganglioglioma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment resulted in partial response 8 weeks after therapy initiation in a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E, but disease progression occurred at 40 weeks due to acquired resistance (PMID: 29880583). | 29880583 | |
| BRAF V600E | melanoma | sensitive | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human melanoma cell line (PMID: 22319199). | 22319199 | |
| BRAF V600E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | IMM-1-104 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, IMM-1-104 treatment led to tumor growth inhibition in a cell line xenograft model of melanoma harboring BRAF V600E (Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P252). | detail... |
| BRAF V600E | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in significant tumor regression in melanoma cell line xenograft models harboring BRAF V600E and demonstrated a 56% (5/9) complete response rate (PMID: 27488531). | 27488531 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI 882370 + Trametinib | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Mekinist (trametinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 |
| BRAF V600E | thyroid gland carcinoma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Tafinlar (dabrafenib) treatment resulted in a partial response in 29% (4/14) and stable disease in 43% (6/14) of patients with thyroid carcinoma harboring BRAF V600E, with 64% (9/14) of patients achieved at least a 10% decrease by RECIST, and a median progression-free survival of 11.3 months among responders (PMID: 25285888; NCT00880321). | 25285888 | |
| BRAF V600E | colon cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | ABM-1310 + Binimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with ABM-1310 and Mektovi (binimetinib) led to inhibition of tumor growth in a colon cancer cell line xenograft model harboring BRAF V600E (Cancer Res (2020) 80 (16_Supplement): 4038). | detail... |
| BRAF V600E | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + SCH772984 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable inhibition of Erk signaling and proliferation of melanoma cells overexpressing BRAF V600E in culture (PMID: 28714990). | 28714990 |
| BRAF V600E | colorectal adenocarcinoma | sensitive | DEL-22379 | Preclinical - Pdx | Actionable | In a preclinical study, DEL-22379 inhibited tumor growth in a colorectal adenocarcinoma patient-derived xenograft model harboring BRAF V600E (PMID: 26267534). | 26267534 | |
| BRAF V600E | thyroid gland cancer | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, thyroid cancer cells harboring BRAF V600E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | thyroid gland cancer | conflicting | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial (Study X2101), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment demonstrated manageable toxicity and resulted in an objective response rate of 25% (9/36, 1 complete response, 8 partial responses) and stable disease in 67% (24/36) of pediatric patients with pretreated low-grade glioma harboring BRAF V600E (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02124772). | detail... |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 69% (9/13, 1 complete response, 6 partial responses, 2 minor responses) in patients with low-grade glioma harboring BRAF V600E, with median duration of response, median progression-free survival, and overall survival time unreached (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | thyroid gland cancer | predicted - sensitive | 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 2 thyroid cancer patients harboring BRAF V600E (1 in dose-escalation phase, 1 in the dose-expansion), and in the dose-expansion phase 1 of 3 thyroid cancer patients harboring a BRAF V600 mutation demonstrated a partial response and 2 demonstrated stable disease, resulting in a disease control rate of 100% (3/3) (PMID: 32182156; NCT02610361). | 32182156 | |
| BRAF V600E | melanoma | sensitive | PLX4720 + Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 demonstrated modest efficacy in patient-derived xenograft models of colorectal cancer harboring BRAF V600E, resulted in tumor growth inhibition or regression, but relapse upon discontinuation of treatment (PMID: 28611205). | 28611205 | |
| BRAF V600E | melanoma | sensitive | PAC-1 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PAC-1 and Zelboraf (vemurafenib) resulted in a synergistic effect when treating melanoma cells harboring BRAF V600E in culture and xenograft models, demonstrating increased apoptosis and decreased tumor volume (PMID: 27297867). | 27297867 | |
| BRAF V600E | 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 in culture (PMID: 32816843). | 32816843 | |
| BRAF V600E | ovarian cancer | predicted - sensitive | 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 | ovarian cancer | predicted - sensitive | 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 | melanoma | sensitive | Encorafenib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928). | 28351928 | |
| BRAF V600E | melanoma | sensitive | Doxorubicin + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Adriamycin (doxorubicin) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and inhibition of cell growth in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | 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 | anaplastic oligodendroglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | melanoma | sensitive | Alpelisib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Alpelisib (BYL719) and PLX4720 enhanced antitumor activity in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Akt signaling in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in a colorectal cancer cell line harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | thyroid gland cancer | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | thyroid gland cancer | sensitive | CLM3 | Preclinical | Actionable | In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression in thyroid cancer cells harboring BRAF V600E in culture (PMID: 24423321). | 24423321 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab + Encorafenib | Phase II | Actionable | In a Phase II (ANCHOR CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment (n=95) demonstrated an acceptable safety profile and resulted in a confirmed response rate of 47.8%, a disease control rate of 88%, a median progression-free survival of 5.8 months, and a median overall survival of 17.2 months in patients with metastatic colorectal cancer harboring BRAF V600E (Ann Oncol Volume 32, Supplement 3, July 2021, Page S222; NCT03693170). | detail... |
| BRAF V600E | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab + Encorafenib | Phase III | Actionable | In a Phase III (BEACON CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment (n=111) resulted in improved median overall survival (9.0 vs 5.4 months, HR=0.52, p<0.001), confirmed response rate (26% vs 2%, p<0.001), and median progression-free survival (4.3 vs 1.5 months, HR=0.38, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). | 31566309 |
| BRAF V600E | glioblastoma | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). | 29247021 | |
| BRAF V600E | thyroid gland cancer | sensitive | Dabrafenib + SCH772984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and SCH772984 synergistically inhibited cell growth of thyroid cancer cell lines harboring BRAF V600E in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 33595872). | 33595872 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). | 25309914 |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a clinical case study, Braftovi (encorafenib) and Mektovi (binimetinib) combination therapy resulted in durable stable disease lasting at least 3.5 years in a patient with low-grade serous ovarian carcinoma harboring BRAF V600E, who was previously treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33043759). | 33043759 |
| BRAF V600E | colorectal cancer | sensitive | BGB-283 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in colorectal cancer cell lines harboring BRAF V600E in culture, and resulted in partial tumor regression in both cell line and patient-derived xenograft models (PMID: 26208524). | 26208524 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of melanoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models of BRAF V600E-positive melanoma, including models with BRAF-inhibitor resistance (PMID: 25873592). | 25873592 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | TW-37 + Vemurafenib | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E | skin melanoma | sensitive | 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 V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... | |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Atezolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab) compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | melanoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation, induced cell-cycle arrest, and inhibited growth of a melanoma cell line harboring BRAF V600E in culture and inhibited tumor growth in cell line xenograft models, and was also effective against cells with acquired resistance to Zelboraf (vemurafenib) or Koselugo (selumetinib) (PMID: 34330842). | 34330842 | |
| BRAF V600E | pleomorphic xanthoastrocytoma | 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with pleomorphic xanthoastrocytoma achieved a partial response lasting 7.2 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | sensitive | CCT196969 | Preclinical - Pdx | Actionable | In a preclinical study, CCT196969 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). | 25500121 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 22281684). | 22281684 | |
| BRAF V600E | anaplastic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dasatinib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) and Mekinist (trametinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | colon neuroendocrine neoplasm | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafinib) treatment of a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation resulted in stable disease for 6 months before disease progression (PMID: 30181415). | 30181415 | |
| BRAF V600E | colon cancer | sensitive | Encorafenib + Panitumumab | Guideline | Actionable | Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination therapy of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in improved clinical symptoms in a patient with epithelioid glioblastoma harboring BRAF V600E, and treatment of the patient's cells resulted in decreased cell viability, reduced phosphorylation of Mek and Erk, increased apoptotic activity compared to either agent alone, and cell cycle arrest in culture, and led to tumor growth suppression in the patient-derived xenograft (PDX) model (PMID: 31345255). | 31345255 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, an epithelioid glioblastoma patient harboring BRAF V600E treated with Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy resulted in stable disease, and the patient continued to demonstrate stable disease at least 16 months after initiation of therapy (PMID: 29632053). | 29632053 |
| BRAF V600E | glioblastoma | sensitive | 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 a complete resolution of symptoms and radiographic partial response after the first treatment in a patient with glioblastoma harboring BRAF V600E whose disease progressed on PLX8394 treatment, and a complete response after 11 months of treatment, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904). | 32923904 |
| BRAF V600E | glioblastoma | sensitive | 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 significant clinical improvement in a patient with epithelioid glioblastoma harboring BRAF V600E, however, her disease progressed after 3 months of therapy (PMID: 31217909). | 31217909 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response in 32% (10/31, 2 complete responses, 8 partial responses) and stable disease in 19% (6/31) of patients with glioblastoma harboring BRAF V600E (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | lung adenocarcinoma | 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with lung adenocarcinoma, 1 achieved a partial response with an ongoing progression-free survival (PFS) at 32.5 mo, 3 patients had stable disease for 15.6, 6.6, and 3.6 mo, and an additional unevaluable patient achieved an 81% reduction of measured lesions and a PFS of 12.7 mo (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | pancreatic acinar cell adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with pancreatic acinar cell carcinoma harboring BRAF V600E who had previously progressed on chemotherapy led to a response at 8 weeks, and ongoing clinical and radiological response was still observed at 32 months of treatment (PMID: 33537843). | 33537843 |
| BRAF V600E | salivary gland carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case report, combined Tafinlar (dabrafenib) and Mekinist (trametinib) treatment of a patient with salivary duct carcinoma harboring BRAF V600E resulted in a reduction of metastatic lesions and stable disease lasting 13 months followed by disease progression (PMID: 30323086). | 30323086 |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Clinical Study | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E achieved an overall response rate of 54% (13/24, 2 complete responses, 11 partial responses, and 10 with stable disease) and a disease control rate of 96% following treatment with Zelboraf (vemurafenib) (PMID: 26200454). | 26200454 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). | detail... | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 43% (6/14, 1 complete response, 5 partial response) in patients with non-small cell lung cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 2 patients (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with non-small cell lung cancer harboring BRAF V600E (n=63) when treated with Zelboraf (vemurafenib), including 23 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring a BRAF V600E mutation had a complete response after treatment with Zelboraf (vemurafenib) (PMID: 23733758). | 23733758 | |
| BRAF V600E | neuroendocrine tumor | predicted - sensitive | 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 a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
| BRAF V600E | colorectal adenocarcinoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of colorectal adenocarcinoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 34330842). | 34330842 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved | Actionable | In 3 Phase II trials (ROAR, NCI-MATCH, X2101) that supported FDA approval, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy demonstrated safety and efficacy in adult and pediatric (6 years or older) patients with advanced solid tumors harboring BRAF V600E (PMID: 34838156, PMID: 32818466, J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002, J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02034110, NCT02465060, NCT02124772). | 32818466 detail... detail... 34838156 detail... detail... |
| BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in an objective response rate of 33.3% (11/33) in patients with advanced solid tumors other than melanoma, thyroid, colorectal, and lung cancer harboring BRAF V600E, with a median duration of response of 12 months, median progression-free survival of 9.4 months, and median overall survival not reached (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002; NCT02465060). | detail... |
| BRAF V600E | melanoma | predicted - sensitive | JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, JSI-1187 treatment in a melanoma cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). | 33568355 |
| BRAF V600E | high grade glioma | sensitive | LY3009120 + Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Zelboraf (vemurafenib) and LY3009120 treatment led to greater inhibition of cell growth compared to either agent alone in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | salivary gland cancer | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), a patient with salivary ductal carcinoma harboring BRAF V600E demonstrated a partial response when treated with Zelboraf (vemurafenib) (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). | detail... 30959471 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | 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 | rectum cancer | sensitive | Encorafenib + Panitumumab | Guideline | Actionable | Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | thyroid gland cancer | sensitive | Ponatinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) and Zelboraf (vemurafenib) treatment synergistically inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 31937621). | 31937621 | |
| BRAF V600E | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E | skin melanoma | sensitive | 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 V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) led to a partial response after 1 month of treatment in a metastatic pancreatic ductal adenocarcinoma patient harboring BRAF V600E, followed by disease progression, which was detected 12 months later (PMID: 35382161). | 35382161 |
| BRAF V600E | glioblastoma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a previously treated pediatric patient with epithelioid glioblastoma harboring BRAF V600E demonstrated stable disease for 10 months when treated with Tafinlar (dabrafenib) (PMID: 29621181). | 29621181 | |
| BRAF V600E | cholangiocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with metastatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to a sustained metabolic response for six months (PMID: 33537843). | 33537843 |
| BRAF V600E | melanoma | sensitive | GDC0879 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GDC0879 inhibited survival of melanoma cell lines harboring BRAF V600E in cell culture, cell line xenograft and patient-derived xenograft (PDX) models (PMID: 19276360). | 19276360 | |
| BRAF V600E | salivary gland carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II (MyPathway) trial, Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with advanced salivary gland carcinoma harboring BRAF V600E, with a progression-free survival of 18.5 months (PMID: 32067683; NCT02091141). | 32067683 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Refametinib (BAY86-9766) inhibited growth of melanoma cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). | 19706763 |
| BRAF V600E | high grade glioma | predicted - sensitive | LY3009120 | Preclinical - Patient cell culture | Actionable | In a preclinical study, LY3009120 treatment led to inhibition of cell viability and growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | glioblastoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). | 26573800 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI 882370 + Trametinib | Preclinical | Actionable | In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). | 26916115 |
| BRAF V600E | colorectal cancer | sensitive | BGB-283 + Cetuximab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 26208524). | 26208524 | |
| BRAF V600E | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 V600E | 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 1 partial response and 3 complete responses in 4 patients with Erdheim-Chester disease harboring BRAF V600E (PMID: 30867592; NCT01953926). | 30867592 |
| BRAF V600E | melanoma | sensitive | LY3214996 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3214996 treatment in a melanoma cell line harboring BRAF V600E led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895). | 31744895 | |
| BRAF V600E | glioblastoma | predicted - sensitive | PLX8394 | Case Reports/Case Series | Actionable | In a clinical case study, PLX8349 treatment resulted in a radiographic partial response and complete resolution of symptoms for 7 months in a patient with glioblastoma harboring BRAF V600E, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904; NCT02428712). | 32923904 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer (PMID: 24523613). | 24523613 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | sensitive | SB590885 | Preclinical - Cell culture | Actionable | In a preclinical study, SB590885 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations (NCCN.org). | detail... |
| BRAF V600E | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) in patients with non-small cell lung cancer harboring BRAF V600E resulted in an overall response rate of 66.7% (38/57) in previously treated patients and 64% (23/36) in untreated patients, versus 33% (26/78) treated with Tafinlar (dabrafenib) alone (PMID: 27080216, PMID: 27283860, PMID: 28919011; NCT01336634). | 27283860 detail... 27080216 detail... detail... 28919011 |
| BRAF V600E | colorectal cancer | sensitive | Erlotinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Tarceva (erlotinib) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E compared to either agent alone (PMID: 22180495). | 22180495 | |
| BRAF V600E | colorectal cancer | sensitive | Erlotinib + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Zelboraf (vemurafenib) and Tarceva (erlotinib) resulted in improved inhibition of tumor growth in BRAF V600E mutant human colon cancer cell line xenograft models compared to either drug as monotherapy (PMID: 22448344). | 22448344 | |
| BRAF V600E | melanoma | sensitive | EBI-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). | 26810733 | |
| BRAF V600E | colon cancer | sensitive | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 | |
| BRAF V600E | colorectal cancer | sensitive | Dabrafenib + Panitumumab | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 | |
| BRAF V600E | colorectal cancer | sensitive | Dabrafenib + Panitumumab | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). | detail... | |
| BRAF V600E | sarcoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in sarcoma patients harboring BRAF V600E (n=6) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 1 patient with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Irinotecan + Vemurafenib | Phase II | Actionable | In a Phase II trial (SWOG1406), addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 vs. 2.0 mo, HR 0.50, p=0.001), response rate (17% vs 4%, p=0.05), and disease control rate (67% vs. 22%, p<0.001) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 33356422; NCT02164916). | 33356422 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Irinotecan + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) and Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 | |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | 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 complete response after 8 months of treatment in a patient with low-grade serous ovarian carcinoma harboring BRAF V600E (PMID: 33043759). | 33043759 |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | 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 a partial response lasting at least 2.5 years in one patient with low grade serous ovarian carcinoma harboring BRAF V600E, and resulted in a complete metabolic response after 4 months of treatment in a second patient (PMID: 35242981). | 35242981 |
| BRAF V600E | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as recurrence therapy for patients with ovarian cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | thyroid gland cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Ganetespib + TAK-733 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). | 24398428 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in melanoma cell lines harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | colon neuroendocrine neoplasm | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Case Reports/Case Series | Actionable | In Phase II trial, Mektovi (binimetinib) therapy in a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation who had previously progressed on Tafinlar (dabrafinib) resulted in disease progression after two cycles (PMID: 30181415; NCT01885195). | 30181415 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + TW-37 | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | melanoma | resistant | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 30104724). | 30104724 | |
| BRAF V600E | lung cancer | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients with lung cancer each harboring BRAF V600E (PMID: 29247021). | 29247021 | |
| BRAF V600E | melanoma | sensitive | 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 cells harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | melanoma | sensitive | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). | 28268064 |
| BRAF V600E | triple-receptor negative breast cancer | predicted - sensitive | Nab-paclitaxel + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) and Abraxane (nab-paclitaxel) combination treatment resulted in regression of some metastatic pulmonary lesions and a progression-free survival of 4.4 months in a patient with triple-negative breast cancer harboring BRAF V600E, but a biopsy in lesions that progressed showed acquisition of additional mutations in PDGFRB, NF2, GRM3, MLH1, FOXA1, LRP1B, and AR amplification (PMID: 34818649). | 34818649 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Panitumumab + Trametinib | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 |
| BRAF V600E | melanoma | sensitive | SBI-755199 | Preclinical | Actionable | In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). | 26603897 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 |
| BRAF V600E | Advanced Solid Tumor | sensitive | BGB-283 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB-283 inhibited viability of a variety of cancer cell lines harboring BRAF V600E in culture (PMID: 26208524). | 26208524 | |
| BRAF V600E | peritoneal serous papillary adenocarcinoma | 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with mucinous-papillary serous adenocarcinoma of the peritoneum achieved a partial response (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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). | 27480103 detail... detail... |
| BRAF V600E | large cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, a patient with poorly differentiated large cell carcinoma harboring BRAF V600E experienced a complete response lasting at least 2 years on combination treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib) (PMID: 35046062). | 35046062 |
| BRAF V600E | melanoma | sensitive | Ulixertinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in melanoma cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). | 28939558 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | colorectal cancer | sensitive | CCT241161 | Preclinical | Actionable | In a preclinical study, CCT241161 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 25500121, PMID: 15294323). | 25500121 15294323 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | SB590885 | Preclinical | Actionable | In a preclinical study, SB590885 inhibited inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF V600E | colorectal cancer | sensitive | Lapatinib + Panobinostat | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) and Faridak (panobinostat) worked synergistically to inhibit growth of BRAF V600E mutant colorectal cancer cells in culture (PMID: 21464044). | 21464044 | |
| BRAF V600E | melanoma | sensitive | TW-37 + Vemurafenib | Preclinical | Actionable | In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E | thyroid gland follicular carcinoma | sensitive | 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 | melanoma | sensitive | Gefitinib + PLX4720 | Preclinical | Actionable | In a preclinical study, Iressa (gefitinib) in combination with PLX4720 inhibited proliferation and tumorigenicity in human melanoma cell line harboring BRAF V600E and resistant to Braf inhibition in culture and in animal models (PMID: 23242808). | 23242808 | |
| BRAF V600E | melanoma | sensitive | DEL-22379 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). | 26267534 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | PLX4720 | Preclinical | Actionable | In a preclinical study, PLX4720 inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF V600E | melanoma | predicted - sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth and tumor regression in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 46% (12/26, 2 complete response, 10 partial response) in patients with advanced solid tumors harboring BRAF V600E, but only 4% (1/23, 1 partial response) in patients harboring non-V600 BRAF mutations (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 33% (56/172) in patients with advanced solid tumors harboring BRAF V600E, including 5 patients with a complete response and 51 patients with a partial response, and led a duration of response of 13.1 months, a progression-free survival of 5.8 months, and an overall survival of 17.6 months (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is in guidelines for patients with advanced or metastatic non-small cell lung cancer with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). | detail... | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Dabrafenib | Phase II | Actionable | In a Phase II trial, 33% (26/78) of previously treated non-small cell lung carcinoma patients harboring BRAF V600E demonstrated an overall response, which included all partial responses, when treated with Tafinlar (dabrafenib) while 67% (4/6) receiving Tafinlar (dabrafenib) as a first-line treatment achieved partial responses (PMID: 27080216; NCT01336634). | 27080216 | |
| BRAF V600E | melanoma | no benefit | RM-018 | Preclinical - Cell culture | Actionable | In a preclinical study, RM-018 did not inhibit growth of melanoma cells harboring BRAF V600E in culture (PMID: 33824136). | 33824136 | |
| BRAF V600E | pancreatic endocrine carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with pancreatic endocrine carcinoma found to harbor BRAF V600E demonstrated stable disease and some tumor shrinkage when treated with Zelboraf (vemurafenib) (PMID: 31158244). | 31158244 | |
| BRAF V600E | colorectal cancer | sensitive | Capecitabine + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Xeloda (capecitabine) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 | |
| BRAF V600E | high grade glioma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and Afinitor (everolimus) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). | 27217440 |
| BRAF V600E | melanoma | decreased response | Pembrolizumab | Clinical Study | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600E | larynx cancer | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in complete response in a patient with larynx cancer harboring BRAF V600E (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF V600E | melanoma | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited cell invasion, cell signaling, and proliferation in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture and in animal models (PMID: 23242808). | 23242808 | |
| BRAF V600E | colorectal cancer | sensitive | PLX7904 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX7904 inhibited survival of colorectal cancer cells harboring BRAF V600E in culture and demonstrated anti-tumor activity in cell line xenograft models (PMID: 26466569). | 26466569 | |
| BRAF V600E | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). | 27488531 |
| BRAF V600E | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
| BRAF V600E | renal cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic renal cell carcinoma harboring BRAF V600E demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26918217). | 26918217 | |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell culture | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of transformed cells over expressing BRAF V600E in culture, while single agent inhibition had no effect (PMID: 26140595). | 26140595 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | colorectal cancer | sensitive | Irinotecan + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO5126766 | Preclinical | Actionable | In a preclinical study, RO5126766 inhibited Mek signaling and increased radioiodide uptake and response in transgenic animal models of papillary thyroid carcinoma driven by BRAF V600E (PMID: 27669459). | 27669459 |
| BRAF V600E | colon cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited Braf V600E in vitro and inhibited growth of human colon cancer cells harboring BRAF V600E in culture (PMID: 21325073, PMID: 24042735). | 24042735 21325073 | |
| BRAF V600E | melanoma | sensitive | BGB659 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | melanoma | predicted - sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring BRAF V600E (PMID: 33953400). | 33953400 | |
| BRAF V600E | melanoma | sensitive | ERAS-007 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation and Erk signaling in a melanoma cell line harboring BRAF V600E in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models, including a Zelboraf (vemurafenib)-resistant PDX model (PMID: 34337566). | 34337566 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a lung cancer cell line harboring BRAF V600E and NF1 T2805I was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell viability (PMID: 31744895). | 31744895 | |
| BRAF V600E | anaplastic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | rectum cancer | sensitive | Cetuximab + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | high grade glioma | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 25% (6/24, 1 complete response, 5 partial responses) in patients with gliomas harboring BRAF V600E, with a median progression free survival of 5.5-months, a median overall survival of 28.2 months (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | high grade glioma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in glioma patients harboring BRAF V600E (n=24) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 5 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| 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). | detail... | |
| BRAF V600E | colorectal cancer | sensitive | EBI-907 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, EBI-907 inhibited BRAF and ERK signaling, resulted in growth inhibition of colorectal cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 26810733). | 26810733 | |
| BRAF V600E | colon cancer | sensitive | 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 | anaplastic pleomorphic xanthoastrocytoma | predicted - sensitive | 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 an ongoing partial response 8 months after initiation of treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, and a near complete response after 3 months of treatment in another patient with relapsed disease (PMID: 28984141). | 28984141 |
| BRAF V600E | melanoma | sensitive | CCT241161 | Preclinical - Pdx | Actionable | In a preclinical study, CCT241161 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). | 25500121 | |
| BRAF V600E | ganglioglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with ganglioglioma harboring BRAF V600E (NCCN.org). | detail... |
| 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 | melanoma | sensitive | SBI-0640726 | Preclinical | Actionable | In a preclinical study, SBI-0640726 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | 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 | sensitive | Erlotinib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Tarceva (erlotinib) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models and culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | melanoma | decreased response | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600E | brain glioblastoma multiforme | predicted - sensitive | 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 tumor shrinkage after 2 months in a patient with epithelioid glioblastoma multiforme harboring BRAF V600E, who had progressed after resection, radiotherapy, and chemotherapy, and following an interruption in therapy due to toxicity demonstrated a partial response and remained progression-free for 19 months, prior to progressing 29 months after initiation of therapy (PMID: 33461766). | 33461766 |
| BRAF V600E | colon cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). | 26343583 | |
| BRAF V600E | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | histiocytic sarcoma | 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 resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with histiocytic sarcoma of the brain achieved a partial response with an ongoing progression-free survival at 20.9 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | lung carcinoma | resistant | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) failed to induce apoptosis in lung carcinoma cells expressing BRAF V600E (PMID: 22649091). | 22649091 | |
| BRAF V600E | colon cancer | sensitive | GDC0879 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). | 19276360 | |
| BRAF V600E | colorectal cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Panitumumab + Trametinib | Phase I | Actionable | In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). | 29431699 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). | 22048237 |
| BRAF V600E | hairy cell leukemia | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) was well tolerated and resulted in an overall response rate of 78% (32/41; 20 complete responses, 12 partial responses) in patients with heavily pretreated recurrent/refractory hairy cell leukemia harboring BRAF V600E, with a 12-month progression-free-survival and overall survival rates of 97.6% and 97.6%, respectively (Blood (2018) 132 (Supplement 1): 391; NCT02034110). | detail... |
| BRAF V600E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + KRT-232 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the addition of KRT-232 (AMG 232) to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a synergistic effect, leading to a greater decrease in tumor growth and tumor size compared to either KRT-232 (AMG 232) alone or Tafinlar (dabrafenib) plus Mekinist (trametinib) in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E (PMID: 32234759). | 32234759 |
| BRAF V600E | skin melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, YM-254890 treatment did not inhibit cell viability of a cutaneous melanoma cell line harboring BRAF V300E in culture (PMID: 33229459). | 33229459 | |
| BRAF V600E | thyroid gland cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). | 27222538 |
| BRAF V600E | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, U0126 treatment inhibited Erk phosphorylation and reduced growth of melanoma cells harboring BRAF V600E in culture (PMID: 18794803). | 18794803 |
| BRAF V600E | intrahepatic cholangiocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with intrahepatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to stable disease at 6 weeks, improvement of lung and liver lesions at 12 weeks after treatment, and response was maintained until disease progression in the liver was observed at 10 months (PMID: 33537843). | 33537843 |
| BRAF V600E | colon adenocarcinoma | not applicable | N/A | Phase III | Emerging | In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). | 26768652 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | melanoma | sensitive | BI-69A11 | Preclinical | Actionable | In a preclinical study, BI-69A11 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). | 20531415 26603897 | |
| BRAF V600E | melanoma | sensitive | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX7904 inhibited survival of melanoma cell lines harboring monomeric BRAF V600E as well as cells harboring the Zelboraf (vemurafenib)-resistant dimeric BRAF V600E in culture (PMID: 26466569). | 26466569 | |
| BRAF V600E | melanoma | sensitive | Cediranib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 and Cediranib (AZD-2171) worked synergistically to inhibit cell growth and induce apoptosis in PLX4720-resistant human melanoma cell lines harboring BRAF V600E in culture and to suppress tumor growth in xenograft models (PMID: 26461489). | 26461489 | |
| BRAF V600E | high grade glioma | predicted - sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of cell viability in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | neuroendocrine tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Zelboraf (vemurafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
| BRAF V600E | melanoma | sensitive | Imatinib + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Gleevec (imatinib) and PLX4720 enhanced antitumor efficacy of melanoma cells harboring BRAF V600E, demonstrating decreased cell survival in xenograft models, and decreased phosphorylation of Mapk1 in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Phase II | Actionable | In a Phase II trial (TAPUR), Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy resulted in an objective response rate of 57% (16/28, 2 complete responses (CR), 14 partial responses (PR)) and a disease control rate (CR + PR + stable disease at 16 wks (SD16+)) of 68% in patients with advanced solid tumors harboring BRAF mutations, and 2 CR, 13 PR, and 2 SD16+ were achieved in a total of 26 patients harboring BRAF V600E (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3008; NCT02693535). | detail... |
| BRAF V600E | colorectal cancer | sensitive | BI 882370 + Cetuximab | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 | |
| BRAF V600E | colorectal cancer | sensitive | Cetuximab + Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Navitoclax + Trametinib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 |
| BRAF V600E | colorectal cancer | sensitive | Bevacizumab + Capecitabine + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment when combined with Xeloda (capecitabine) and Avastin (bevacizumab) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). | 22180495 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Preclinical | Actionable | In a preclinical study, Refametinib (BAY86-9766) inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). | 19706763 |
| BRAF V600E | anaplastic astrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in 1 of 5 patients with anaplastic astrrocytoma harboring BRAF V600E, with 2 other patients achieved stable disease lasting 14.9, and 5.6 months, respectively (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, RO5126766 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). | 26438159 |
| BRAF V600E | melanoma | predicted - sensitive | 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 V600E | melanoma | predicted - sensitive | PF-07284890 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PF-07284890 treatment led to inhibition of tumor growth, tumor regression, and survival benefit in an intracranial model, and tumor growth inhibition in a subcutaneous cell line xenograft model of melanoma harboring BRAF V600E (Cancer Res 2021;81(13_Suppl):Abstract nr 1473). | detail... | |
| BRAF V600E | ganglioglioma | predicted - sensitive | 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 anaplastic ganglioglioma harboring BRAF V600E who stayed on treatment for 13.8 months (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | melanoma | sensitive | PLX4720 + Tivozanib | Preclinical | Actionable | In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 | |
| BRAF V600E | uveal melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed mouse melanocytes expressing BRAF V600E were insensitive to treatment with YM-254890 (PMID: 33229459). | 33229459 | |
| 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 | colorectal cancer | sensitive | DT01 + Fluorouracil + Oxaliplatin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DT01 increased sensitivity of human colorectal cancer (CRC) cells harboring BRAF V600E to Eloxatin (oxaliplatin) and Adrucil (5-fluorouracil), and the combination resulted in decreased liver tumor growth in CRC cell line xenograft metastasis models (PMID: 26637369). | 26637369 | |
| BRAF V600E | melanoma | sensitive | 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 | colon cancer | predicted - sensitive | ABM-1310 + Cetuximab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with ABM-1310 and Erbitux (cetuximab) led to inhibition of tumor growth in a colon cancer cell line xenograft model harboring BRAF V600E (Cancer Res (2020) 80 (16_Supplement): 4038). | detail... | |
| BRAF V600E | 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 BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with epithelioid glioblastoma harboring BRAF V600E continued to response as Cotellic (cobimetinib) was added to Zelboraf (vemurafenib) treatment (PMID: 31217909). | 31217909 |
| BRAF V600E | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | melanoma | sensitive | INU-152 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INU-152 reduced MEK and ERK phosphorylation and growth of a melanona cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 28645859). | 28645859 | |
| BRAF V600E | colon cancer | sensitive | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 | |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E experienced progressive disease after response to treatment Zelboraf (vemurafenib), and was found to have acquired NRAS Q61K (PMID: 34376578). | 34376578 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | ASTX029 | Preclinical - Cell culture | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of a melanoma cell line harboring BRAF V600E and expressing NRAS Q61K in culture (PMID: 34330842). | 34330842 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | XL888 | Preclinical | Actionable | In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). | 22351686 | |
| BRAF V600E NRAS Q61K | colorectal cancer | predicted - resistant | 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 40 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS Q61K was identified as an acquired mutation at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS Q61K | lung adenocarcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). | 29631033 |
| BRAF V600E PDGFRB over exp | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and overexpressing Pdgfrb demonstrated resistance to Mekinist (trametinib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E PDGFRB over exp | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and overexpressing Pdgfrb demonstrated resistance to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E PDGFRB over exp | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, over expression of PDGFRB conferred acquired resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 | |
| BRAF V600E PDGFRB over exp | melanoma | sensitive | XL888 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with XL888 increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant human melanoma cell lines harboring a BRAF V600E mutation and over expression of PDGFRB in cell culture and in xenograft models (PMID: 22351686). | 22351686 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to Zelboraf (vemurafenib) in melanoma cell lines harboring BRAF V600, resulting in decreased sensitivity to Zelboraf (vemurafenib)-induced inhibition of MAPK pathway activation and cell proliferation in culture (PMID: 24448821). | 24448821 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient harboring BRAF V600E demonstrated an initial response to treatment with Zelboraf (vemurafenib), but progressed following emergence of a MAP2K1 C121S mutation (PMID: 21383288). | 21383288 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 C121S | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell line harboring BRAF V600E mutation and overexpressing MAP2K1 C121S in culture (PMID: 24448821). | 24448821 |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 C121S conferred resistance to PLX4720 in melanoma cells harboring BRAF V600E in culture (PMID: 21383288). | 21383288 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 C121S conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 C121S was resistant to Mekinist (trametinib) in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 C121S | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E mutation and overexpressing MAP2K1 C121S were less sensitive than those overexpressing wild-type MAP2K1 to Selumetinib (AZD6244)-induced inhibition of Mapk pathway activation and cell proliferation in culture (PMID: 24448821). | 24448821 |
| BRAF V600E MAP2K1 C121S | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VX-11e, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
| BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | Cetuximab + Regorafenib | Preclinical | Actionable | In a preclinical study, the combination of Erbitux (cetuximab) and Stivarga (regorafenib) inhibited growth, reduced Akt and Mapk phosphorylation, and induced apoptosis of human colorectal cancer cell lines harboring BRAF V600E and PIK3CA P449T in culture (PMID: 25838391). | 25838391 | |
| BRAF V600E PIK3CA P449T | colorectal cancer | resistant | Cetuximab | Preclinical | Actionable | In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Erbitux (cetuximab) in culture (PMID: 25838391). | 25838391 | |
| BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
| BRAF V600E PIK3CA P449T | 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 and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
| BRAF V600E PIK3CA P449T | colorectal cancer | resistant | Regorafenib | Preclinical | Actionable | In a preclinical study, human colorectal cancer cells harboring BRAF V600E and PIK3CA P449T were resistant to Stivarga (regorafenib) in culture (PMID: 25838391). | 25838391 | |
| BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
| BRAF V600E NRAS G12V | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E NRAS G12V | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 L115P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115P in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture, likely due to the acquired secondary resistance mutation MAP2K1 L115P (PMID: 27312529). | 27312529 |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Alpelisib + Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 L115P | melanoma | conflicting | 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 V600E and expressing MAP2K1 L115P in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical | Actionable | In a preclinical study, over expression of MAPK21 L115P in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 |
| BRAF V600E MAP2K1 L115P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 L115P in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 I103N | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and expressing MAP2K1 I103N in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 I103N in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 I103N | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical | Actionable | In a preclinical study, over expression of MAPK21 I103N in melanoma cells harboring BRAF V600E resulted in insensitivity to growth inhibition by PD-0325901 in cell culture (PMID: 26267534). | 26267534 |
| BRAF V600E MAP2K1 V211D | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (Ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 V211D | 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 secondary resistant mutation of MAP2K1 V211D (PMID: 27312529). | 27312529 |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to CI-1040 (PD184352) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and Mekinist (trametinib) in culture (PMID: 27312529). | 27312529 |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 V211D in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture (PMID: 27312529). | 27312529 |
| BRAF V600E MAP2K1 V211D | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | 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 V600E, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | no benefit | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) did not improve the response to human melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS A146T | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E and also had reduced sensitivity in comparison to cell lines harboring BRAF V600E and NRAS A146T in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were >10-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS A146T | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | 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 V600E and NRAS A146T in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | conflicting | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 K59del | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del in culture, compared to either agent alone (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and MAP2K1 K59del were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 K59del | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E harboring MAP2K1 K59del in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | 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 V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 Q56P | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 Q56P | melanoma | conflicting | 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 V600E and expressing MAP2K1 Q56P in culture (PMID: 28986383). | 28986383 |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, expression of MAP2K1 Q56P in melanoma cells harboring BRAF V600E conferred resistance to PLX4720 treatment in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 Q56P in melanoma cells harboring BRAF V600E conferred resistance to Koselugo (selumetinib) treatment in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 Q56P was resistant to Zelboraf (vemurafenib) in culture (PMID: 28986383). | 28986383 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 Q56P | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Talfinlar (dabrafenib) and Mekinist (trametinib) resulted in improved growth inhibition in melanoma cells harboring BRAF V600E and expressing MAP2K1 Q56P in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K NRAS A146T | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF V600E CSF1R pos | melanoma | sensitive | Pexidartinib + Vemurafenib | Preclinical | Actionable | In a preclinical study, a melanoma mouse model harboring BRAF V600E treated with Zelboraf (vemurafenib) demonstrated a greater drug induced sensitivity when treatment was combined with PLX3397, resulting in increased infiltration of lymphocytes via Csf1r inhibition and elevated antitumor activity (PMID: 25939769). | 25939769 | |
| BRAF V600E PTEN loss | melanoma | sensitive | GDC0879 + Pictilisib | Preclinical - Cell culture | Actionable | In a preclinical study, GDC0879 and Pictilisib (GDC-0941) synergistically inhibited survival of melanoma cell lines harboring BFAF V600E and PTEN loss in cell culture (PMID: 19276360). | 19276360 | |
| BRAF V600E PTEN loss |