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| Profile Name | BRAF E586K |
| Gene Variant Detail | |
| Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor LY3009120 |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF G466E | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | melanoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E HRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of a melanoma cell line harboring BRAF G466E and HRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF G606E | Advanced Solid Tumor | no benefit | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G606E (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF G469L | lung adenocarcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring BRAF G469L did not respond to Zelboraf (vemurafenib) therapy (PMID: 24035431). | 24035431 | |
| BRAF mutant | melanoma | sensitive | Tubastatin A | Preclinical | Actionable | In a preclinical study, Tubastatin A inhibited proliferation of BRAF mutant melanoma cell lines in culture (PMID: 25957812). | 25957812 | |
| BRAF mutant | colorectal cancer | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Case Reports/Case Series | Actionable | In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). | 22048237 |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). | 28363909 | |
| BRAF mutant | melanoma | sensitive | S63845 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Zelboraf (vemurafenib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Zelboraf (vemurafenib) alone (PMID: 27760111). | 27760111 | |
| BRAF mutant | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). | 28775144 | |
| BRAF mutant | Advanced Solid Tumor | no benefit | LY3009120 | LY3009120 | Case Reports/Case Series | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 5 of 12 patients with advanced or metastatic cancer harboring BRAF mutations (PMID: 31645440; NCT02014116). | 31645440 |
| BRAF mutant | colon cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Selumetinib (AZD6244) resulted in some reduced cell growth in colon cancer cells harboring a BRAF mutation in culture (PMID: 27655129). | 27655129 |
| BRAF mutant | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). | 23039341 |
| BRAF mutant | melanoma | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 blocked survival and growth of vemurafenib/PLX4720-resistant melanoma cells harboring BRAF V600E splice variants in culture (PMID: 24422853). | 24422853 | |
| BRAF mutant | melanoma | predicted - sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021). | 29247021 | |
| BRAF mutant | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of BRAF-mutant melanoma cell lines in culture, and inhibited tumor growth melanoma cell line xenograft models harboring BRAF mutations, including models with BRAF inhibitor resistance (PMID: 25873592). | 25873592 |
| BRAF mutant | Advanced Solid Tumor | sensitive | RAF709 | Phase I | Actionable | In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). | 29343524 | |
| BRAF mutant | pancreatic adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | melanoma | sensitive | MEK1 Inhibitor | E6201 + LY294002 | Preclinical | Actionable | In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). | 23039341 |
| BRAF mutant | colorectal cancer | no benefit | Regorafenib | Phase II | Actionable | In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). | 30120161 | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | LXH 254 | Case Reports/Case Series | Actionable | In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). | detail... | |
| BRAF mutant | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZ628 + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) and AZ628 synergistically inhibited Mapk signaling and cell proliferation in BRAF mutant colorectal cancer cell lines in culture (PMID: 26351322). | 26351322 |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... | |
| BRAF mutant | cervix carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | melanoma | predicted - sensitive | UNC2025 + Vemurafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Zelboraf (vemurafenib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring a BRAF mutation in culture and led to a higher degree of tumor growth inhibition in a patient derived xenograft (PDX) model of melanoma with a BRAF mutation when compared to either therapy alone (PMID: 30482852). | 30482852 | |
| BRAF mutant | melanoma | sensitive | MLN2480 | Phase I | Actionable | In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). | detail... | |
| BRAF mutant | melanoma | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). | 26140595 | |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). | 28611205 | |
| BRAF mutant | colorectal cancer | decreased response | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). | 26351322 | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in BRAF-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 |
| BRAF mutant | splenic marginal zone lymphoma | not applicable | N/A | Guideline | Diagnostic | BRAF mutations aid in the diagnosis of splenic marginal zone lymphoma (NCCN.org). | detail... | |
| BRAF mutant | Advanced Solid Tumor | sensitive | Dabrafenib | Phase I | Actionable | In a Phase I clinical trial, Tafinlar (dabrafenib) demonstrated safety and efficacy in patients with BRAF V600E positive solid tumors (PMID: 22608338). | 22608338 | |
| BRAF mutant | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). | 22460902 | |
| BRAF mutant | colorectal cancer | predicted - sensitive | SY-5609 | Preclinical - Pdx | Actionable | In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). | detail... | |
| BRAF mutant | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Panitumumab + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). | 27770002 |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). | 28947956 |
| BRAF mutant | thyroid gland cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase I | Actionable | In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027). | 23406027 |
| BRAF mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in a patients with BRAF-mutant melanoma in a dose escalation study, and partial response in 33% (2/6) of BRAF-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... | |
| BRAF mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | MLN2480 | Preclinical - Cell culture | Actionable | In a preclinical study, MLN2480 inhibited downstream signaling and proliferation of several BRAF mutant solid tumor cell lines in culture (EJC Supp, Nov 2010, Vol 8(7), p40-41). | detail... | |
| BRAF mutant | colon cancer | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). | 26140595 | |
| BRAF mutant | melanoma | sensitive | PET-16 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). | 26984758 | |
| BRAF mutant | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | multiple myeloma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | melanoma | sensitive | Buparlisib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Encorafenib (LGX818) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 | |
| BRAF mutant | pancreatic cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 | |
| BRAF mutant | colorectal cancer | sensitive | Belvarafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| BRAF mutant | melanoma | sensitive | Vemurafenib + Voruciclib | Phase I | Actionable | In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). | detail... | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation demonstrated greater sensitivity to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture when compared to either agent alone (PMID: 27488531). | 27488531 |
| BRAF mutant | colorectal cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in an estimated progression free survival of 1.4 months and overall survival of 7.1 months in colorectal cancer patients harboring BRAF mutations (PMID: 28152546). | 28152546 |
| BRAF mutant | colorectal cancer | predicted - sensitive | LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 resulted in a disease control rate of 8.3% (1/12) in BRAF mutant patient-derived xenograft models of colorectal cancer (PMID: 28611205). | 28611205 | |
| BRAF mutant | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, a majority of human colorectal cancer cell lines (4/7) harboring mutant BRAF were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | Advanced Solid Tumor | decreased response | XL147 | Preclinical | Actionable | In a preclinical study, tumor cell lines harboring BRAF mutations demonstrated limited sensitivity to XL147 treatment in culture (PMID: 25637314). | 25637314 | |
| BRAF mutant | melanoma | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring a BRAF mutation resulted in inhibition of brain tumor growth (PMID: 27307593). | 27307593 | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... | |
| BRAF mutant | lymphoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF mutant | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF mutant | thyroid gland cancer | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| BRAF mutant | melanoma | sensitive | Encorafenib | Phase I | Actionable | In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). | 28611198 | |
| BRAF mutant | colorectal cancer | sensitive | Alpelisib + Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). | detail... 28363909 | |
| BRAF mutant | melanoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... | |
| BRAF mut NRAS mut | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). | 26169970 | |
| BRAF mut NRAS mut | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). | 25873592 |
| BRAF mut NRAS wild-type | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). | 26169970 | |
| BRAF mut STAG2 dec exp | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) in culture (PMID: 27500726). | 27500726 |
| BRAF mut STAG2 dec exp | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Tafinlar (dabrafenib) in culture (PMID: 27500726). | 27500726 | |
| BRAF mut STAG2 dec exp | melanoma | decreased response | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cell lines resulted in decreased response to Zelboraf (vemurafenib) both in culture and in cell line xenograft models (PMID: 27500726). | 27500726 | |
| BRAF mut STAG2 dec exp | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, decreasing Stag2 expression level through shRNA knockdown in BRAF mutated melanoma cells resulted in decreased response to Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment in culture (PMID: 27500726). | 27500726 |
| BRAF mut RB1 loss | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| BRAF mut RB1 loss | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation and RB1 loss demonstrated reduced sensitivity when treated with Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| BRAF mut RB1 loss | melanoma | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). | 27488531 | |
| BRAF mut PTPN11 dec exp | colorectal cancer | sensitive | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, knocking down of Ptpn11 expression via shRNA sensitized BRAF mutant colorectal cancer cell lines to PLX4720 in culture (PMID: 26351322). | 26351322 | |
| BRAF mut PIK3CA wild-type | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | TAK-733 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, mutations in BRAF, KRAS, or NRAS were associated with sensitivity to TAK-733 in colorectal cancer cell lines in culture, and patient-derived xenograft models harboring KRAS or BRAF mutations with wild-type PIK3CA demonstrated a trend toward higher tumor growth inhibition following TAK-733 treatment (PMID: 26439693). | 26439693 |
| BRAF mut IDH1 wild-type | glioblastoma multiforme | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). | 30742119 | |
| BRAF mut IDH1 wild-type | glioblastoma multiforme | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). | 30742119 | |
| BRAF 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 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 - 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 F247L | Advanced Solid Tumor | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Tafinlar (dabrafenib) in culture (PMID: 28512244). | 28512244 | |
| BRAF F247L | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing BRAF F247L demonstrated sensitivity to Mekinist (trametinib) in culture (PMID: 28512244). | 28512244 |
| BRAF K601E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). | 23248257 |
| BRAF K601E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). | 28344857 |
| BRAF K601E | melanoma | no benefit | Dabrafenib | Phase I | Actionable | In a Phase I trial, no responses were demonstrated among three melanoma patients with non-V600 BRAF mutations, including two patients harboring BRAF K601E, following treatment with Tafinlar (dabrafenib), compared to a confirmed response rate of 50% in patients harboring BRAF V600 mutations (PMID: 22608338). | 22608338 | |
| BRAF K601E | 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 K601E, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601E (PMID: 26343582). | 26343582 | |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 | |
| BRAF K601E | Advanced Solid Tumor | conflicting | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 6 of the non-responding patients harbored BRAF K601E (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF K601E | pancreatic endocrine carcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 31158244). | 31158244 |
| BRAF K601E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). | 22798288 |
| BRAF K601E | prostate adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in a near partial response in a patient with prostate adenocarcinoma harboring BRAF K601E until disease progression at 9.7 months (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF K601E | pancreatic endocrine carcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 31158244). | 31158244 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 | |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF K601E MAP2K1 V211D | colon cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | sensitive | MEK inhibitor (Pan) | MAP855 | Preclinical - Pdx | Actionable | In a preclinical study, MAP955 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). | 31227518 |
| BRAF 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 | lung adenocarcinoma | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Patient cell culture | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 combination treatment resulted in significant apoptosis in primary tumor cells isolated from a lung adenocarcinoma patient harboring BRAF N581S in culture (PMID: 26140595). | 26140595 | |
| BRAF N581S | 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 | 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 | |
| APC Q1429fs BRAF N581S ERBB2 L755S | rectum adenocarcinoma | no benefit | Fluorouracil + Leucovorin + Trastuzumab | Case Reports/Case Series | Actionable | In a clinical case study, a rectal adenocarcinoma patient harboring APC Q1429fs, BRAF N581S, and ERBB2 L755S did not respond to Herceptin (trastuzumab) treatment in combination with Fluorouracil and Wellcovorin (leucovorin) (PMID: 27626067). | 27626067 | |
| BRAF N486_P490del | lymphatic system cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). | 32991018 |
| BRAF N486_P490del | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). | 26732095 |
| BRAF N486_P490del | pancreatic cancer | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with pancreatic cancer harboring BRAF N486_P490del had a partial response when treated with Tafinlar (dabrafenib), demonstrating a decrease in both the size of the primary and metastatic lesions and response duration of 6 months (PMID: 31519698). | 31519698 | |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). | 29903880 |
| BRAF N486_P490del | ovarian cancer | sensitive | LY3009120 | LY3009120 | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to LY3009120, resulting in inhibition of cell growth and decreased phosphorylation of MEK and ERK in culture (PMID: 26732095). | 26732095 |
| BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was resistant to Zelboraf (vemurafenib), resulting in minimal inhibition of both cell growth and phosphorylation of MEK and ERK in culture (PMID: 26732095). | 26732095 | |
| BRAF N486_P490del | ovarian cancer | predicted - resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) resulted in minimal growth inhibitory activity of an ovarian cancer cell line harboring BRAF N486_P490del (PMID: 26732095). | 26732095 | |
| BRAF 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 act mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 | |
| BRAF act mut | colorectal cancer | no benefit | Venetoclax + VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 | |
| BRAF act mut | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). | 24422853 | |
| BRAF act mut | thyroid gland cancer | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) therapy is included in guidelines for differentiated thyroid carcinoma patients with recurrent, advanced, or metastatic disease harboring BRAF activating mutations, in cases that are not surgically resectable or amenable to radioactive iodine (NCCN.org). | detail... | |
| BRAF act mut | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Phase I | Actionable | In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). | 23489023 | |
| BRAF act mut | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). | detail... |
| BRAF act mut | thyroid gland cancer | sensitive | Vemurafenib | Phase I | Actionable | In a Phase I trial, Zelboraf (vemurafenib) demonstrated safety and efficacy in metastatic papillary thyroid cancer patients carrying BRAF activating mutations (PMID: 23489023). | 23489023 | |
| BRAF act mut | thyroid gland cancer | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) therapy is included in guidelines for differentiated thyroid carcinoma patients with recurrent, advanced, or metastatic disease harboring BRAF activating mutations, in cases that are not surgically resectable or amenable to radioactive iodine (NCCN.org). | detail... | |
| BRAF act mut | lung non-small cell carcinoma | sensitive | RAF709 | Preclinical - Pdx | Actionable | In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). | 29343524 | |
| BRAF act mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). | 22084396 |
| BRAF act mut | colorectal cancer | predicted - sensitive | VX-11e + WEHI-539 | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). | 27974663 | |
| BRAF act mut | melanoma | no benefit | Sorafenib | Phase II | Actionable | In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). | 22394203 16880785 | |
| BRAF F595L | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with Zelboraf (vemurafenib) did not reduce activation of Mek and Erk by BRAF F595L in transformed cells in culture (PMID: 26582644). | 26582644 | |
| BRAF 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 | 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 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 | |
| BCORL1 Q1076H BRAF V47_D380del BRAF V600E | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E was found to have BRAF V47_D380del and BCORL1 Q1076H mutations after acquiring resistance to Zelboraf (vemurafenib), and expression of BRAF V47_D380del and BCORL1 Q1076H in a BRAF V600E-positive melanoma cell line resulted in decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 29605720). | 29605720 | |
| BRAF P731T | 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, 1 of the non-responding patients harbored BRAF P731T (PMID: 29320312; NCT02091141). | 29320312 | |
| 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 | 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 | 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 | 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 K601T | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601T (PMID: 26343582). | 26343582 | |
| BRAF G466V | lung adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G466V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G466V | lung cancer | predicted - sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of lung cancer cells harboring BRAF G466V in culture (PMID: 30104724). | 30104724 | |
| BRAF G466V | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Mekinist (trametinib) delayed tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 |
| BRAF G466V | lung non-small cell carcinoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 27523909). | 27523909 | |
| BRAF G466V | lung adenocarcinoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G466V in culture (PMID: 27834212). | 27834212 | |
| BRAF G466V | colorectal cancer | no benefit | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit ERK signaling or tumor growth in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 | |
| BRAF G466V | colorectal cancer | predicted - sensitive | Irinotecan + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan) (PMID: 28783719). | 28783719 | |
| BRAF G466V | 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, 1 of the non-responding patients harbored BRAF G466V (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF G466V | colorectal cancer | sensitive | Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 | |
| BRAF G466V | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a non-small cell lung cancer cell line harboring BRAF G466V in culture (PMID: 28947956). | 28947956 |
| BRAF G466V | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). | 28783719 |
| BRAF G466V | Advanced Solid Tumor | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with tumor of unknown primary harboring BRAF G464V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G466V | lung non-small cell carcinoma | sensitive | TAE226 | Preclinical | Actionable | In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring BRAF G466V mutation in culture (PMID: 26090892). | 26090892 | |
| BRAF G466V | lung non-small cell carcinoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung cancer cells expressing BRAF G466V in culture (PMID: 22649091). | 22649091 | |
| BRAF G466V | lung 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 G466V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF G466V | lung non-small cell carcinoma | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring BRAF G466V demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF G466V NRAS Q61K | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF 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 | 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 | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF V600K | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first or second-line therapy in patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation (PMID: 30715168, PMID: 30285222; ESMO.org). | 30715168 detail... 30285222 |
| 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 | 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 | 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 | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600K (n=19) had increased tumor mutational burden and greater response rates (53% vs. 29%, p=0.059), progression-free survival (19 vs. 2.7 months, p=0.049), and overall survival (20.4 vs. 11.7 months, p=0.081) relative to patients with BRAF V600E (n=84) when treated with Keytruda (pembrolizumab) (n=17 and 62 for BRAF V600K and V600E, respectively) or Opdivo (nivolumab) (n=2 and 22 for BRAF V600K and V600E, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600K | skin melanoma | sensitive | 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 | 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 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 | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | 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 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 | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124Q | melanoma | sensitive | VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 |
| BRAF V600K MAP2K1 P124L | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K 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 G464V | lung adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G464V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G464V | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464V (PMID: 26343582). | 26343582 | |
| BRAF G464V | Advanced Solid Tumor | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF 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 | 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 | colorectal cancer | no benefit | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). | 22281684 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | glioblastoma multiforme | sensitive | BI2536 + PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). | 26573800 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | glioblastoma multiforme | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). | 29247021 | |
| BRAF V600E | 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 | 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 | 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 | 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 | 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 | 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 | PLX4720 + Tivozanib | Preclinical | Actionable | In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). | 26461489 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) decreased tumor growth in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 23942066). | 23942066 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | INU-152 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, INU-152 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture, and reduced tumor growth in BRAF V600E-mutant colorectal cancer cell line xenograft models (PMID: 28645859). | 28645859 | |
| BRAF V600E | colorectal cancer | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | glioblastoma multiforme | sensitive | BI2536 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). | 26573800 | |
| BRAF V600E | 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 | 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 | 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 | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human melanoma cell line (PMID: 22319199). | 22319199 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | colorectal cancer | sensitive | SCH772984 | Preclinical | Actionable | In a preclinical study, SCH772984 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | colon cancer | sensitive | GDC0879 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). | 19276360 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | thyroid gland papillary carcinoma | predicted - 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 and progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844). | 20818844 | |
| 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 | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Refametinib | Preclinical | Actionable | In a preclinical study, Refametinib (BAY86-9766) inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture and suppressed tumor growth in cell line xenograft models (PMID: 19706763). | 19706763 |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). | 27488531 |
| BRAF V600E | melanoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). | 26267534 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | glioblastoma multiforme | 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 multiforme | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | glioblastoma multiforme | decreased response | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). | 26573800 | |
| BRAF V600E | 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 | biliary tract cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial, 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | malignant 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 | 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 | CCT241161 | Preclinical - Pdx | Actionable | In a preclinical study, CCT241161 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). | 25500121 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | predicted - sensitive | RAF265 | Phase I | Actionable | In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). | 28719152 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | Phase II | Actionable | In a Phase II clinical trial (VE-BASKET), Zelboraf (vemurafenib) treatment of BRAF V600E mutant pleomorphic xanthoastrocytomas resulted in a 42.9% (3/7) objective response rate, a 5.7-month median progression-free survival, and best overall response rates of 14.3% (1/7) for complete response, 28.6% (2/7) for partial response, and 42.9% (3/7) for stable disease (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | glioblastoma multiforme | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). | 26573800 |
| BRAF V600E | 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 | melanoma | sensitive | LY3009120 | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). | 26343583 |
| BRAF V600E | 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 | 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 | 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 | 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 | 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 | 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 | 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 | malignant glioma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and Afinitor (everolimus) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). | 27217440 |
| BRAF V600E | malignant 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 | malignant glioma | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial (VE-BASKET), treatment of patients with gliomas harboring BRAF V600E mutations with Zelboraf (vemurafenib) resulted in a 25% (6/24) objective response rate, 5.5-month median progression free survival, 28.2 month median overall survival, and best overall response rates of 4.2% (1/24) for complete response, 20.8% (5/24) for partial response, and 41.7% (10/24) for stable disease (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). | 22048237 |
| BRAF V600E | melanoma | 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 | glioblastoma multiforme | predicted - 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 multiforme | 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 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 | 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 | 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 | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, RO5126766 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). | 26438159 |
| BRAF V600E | colorectal cancer | sensitive | Dabrafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation had increased sensitivity to Tafinlar (dabrafenib) in culture compared to cell lines with wild-type BRAF (PMID: 24885690). | 24885690 | |
| BRAF V600E | melanoma | sensitive | PLX4720 + Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | colon adenocarcinoma | not applicable | N/A | Phase III | Emerging | In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). | 26768652 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 69% (11/16; 1 complete response and 10 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E (PMID: 29072975; NCT02034110). | 29072975 detail... 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 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 | 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 | 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 | colon cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). | 16273091 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Ganetespib + TAK-733 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). | 24398428 |
| BRAF V600E | 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 | melanoma | sensitive | DETD-35 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 and Zelboraf (vemurafenib) synergistically inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). | 27048951 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | 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 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 | 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 | 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 | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). | 24422853 | |
| BRAF V600E | melanoma | sensitive | 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 | colorectal cancer | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). | 24885690 | |
| BRAF V600E | melanoma | sensitive | Navitoclax + Vemurafenib | Preclinical | Actionable | In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). | 25665005 | |
| BRAF V600E | melanoma | 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 | 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 | glioblastoma multiforme | predicted - 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 | DEL-22379 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). | 26267534 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | malignant glioma | predicted - sensitive | Everolimus + PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 | |
| BRAF V600E | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | melanoma | sensitive | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | 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 response, 24 partial response), and inhibited phosphorylation of Erk and Ccnd1, and reduced cell proliferation in metastatic melanoma patients harboring BRAF V600E (PMID: 20818844). | 20818844 | |
| 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 | 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 | 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 | colorectal cancer | sensitive | Regorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). | 21170960 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI 882370 + Trametinib | Preclinical | Actionable | In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). | 26916115 |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | 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 | 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 NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS Q61K | melanoma | sensitive | 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 | 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 | 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 | 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 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 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 | 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 | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 C121S | melanoma | sensitive | VRT11E | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 C121S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 C121S | melanoma | resistant | 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, 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 | 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 | 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 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 + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA P449T in culture (PMID: 23629727). | 23629727 |
| BRAF V600E PIK3CA P449T | colorectal cancer | sensitive | 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 + 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 | 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 NRAS G12V | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, expression of NRAS G12V in melanoma cells harboring BRAF V600E conferred resistance to Zelboraf (vemurafenib) in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E NRAS G12V | melanoma | sensitive | DEL-22379 | Preclinical - Cell culture | Actionable | In a preclinical study, DEL-22379 inhibited growth of a melanoma cell line harboring BRAF V600E and over expressing NRAS G12V in culture (PMID: 26267534). | 26267534 | |
| BRAF V600E MAP2K1 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 | 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 | 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 | 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 | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | Cetuximab + Dabrafenib + SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Tafinlar (dabrafenib), and SCH772984 inhibited survival of colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 L115P mutation and subsequent resistance to Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 L115P | melanoma | 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 | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 L115P in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 L115P | colorectal cancer | sensitive | 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 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 | 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 | 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 L115P demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| 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 | 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 | 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 | colorectal cancer | resistant | Cetuximab + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired a MAP2K1 V211D mutation and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E MAP2K1 V211D | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V211D demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 V211D | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by Selumetinib (AZD6244) in cell culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 V211D | 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 | 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 | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K V211D demonstrated resistance to growth inhibition by CI-1040 in cell culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 V211D | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + 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 | 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 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 | 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 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 | 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 | 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 | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | 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 | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | decreased response | 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 | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E and NRAS A146T were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E NRAS A146T | melanoma | sensitive | 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 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 | 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 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 | 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 | conflicting | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 | |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | 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 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 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 | 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 | 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 | 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 | 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 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 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 | 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 | 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 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 | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing MAP2K1 Q56P displayed reduced sensitivity to Mekinist (trametinib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 Q56P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the MEK inhibitor, Koselugo (selumetinib), in cell culture (PMID: 19915144). | 19915144 |
| 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 | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, melanoma cells harboring the MAP2K1 Q56P mutation in the presence of BRAF V600E were resistant to the B-RAF inhibitor PLX4720 in culture (PMID: 19915144). | 19915144 | |
| BRAF V600E MAP2K1 Q56P | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PLX4720 + Selumetinib | Preclinical | Actionable | In a preclinical study, combined treatment with selumetinib and PLX4720 strongly suppressed the emergence of resistant MAP2K1 mutations in BRAF V600E cells in culture (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 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 T529N BRAF V600E | Advanced Solid Tumor | conflicting | Sorafenib | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to Nexavar (sorafenib)-mediated inhibition of Erk phosphorylation but were equally as sensitive to Nexavar (sorafenib)-mediated growth inhibition as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | resistant | SB590885 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to SB590885 in culture (PMID: 20538618). | 20538618 | |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). | 20538618 |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | resistant | PLX4720 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to PLX4720 in culture (PMID: 20538618). | 20538618 | |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | resistant | RAF265 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to RAF265 in culture (PMID: 20538618). | 20538618 | |
| BRAF V600E MAP2K1 H119P | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E treated with Selumetinib (AZD6244) in culture demonstrated resistance, which was a result of the resistance mutation, MAP2K1 H119P (PMID: 19915144). | 19915144 |
| BRAF V600E MAP2K1 V60E | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 V60E | melanoma | sensitive | VRT11E | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 V60E demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 P124S | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and MAP2K1 P124S demonstrated decreased sensitivity to Selumetinib (AZD6244) compared to cells harboring BRAF V600E alone in culture (PMID: 22197931). | 22197931 |
| BRAF V600E MAP2K1 P124S | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 24265153). | 24265153 |
| BRAF V600E MAP2K1 P124S | melanoma | sensitive | VRT11E | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124S demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Tafinlar (dabrafenib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, MAP2K1 G128V conferred resistance to the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) in BRAF V600E-mutant melanoma cells in culture (PMID: 24265154). | 24265154 |
| BRAF V600E MAP2K1 G128V | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated resistance to treatment with Mekinist (trametinib) in culture, resulting in sustained Map2k1/2 and Erk1/2 phosphorylation (PMID: 24265153). | 24265153 |
| BRAF V600E MAP2K1 G128V | melanoma | sensitive | VRT11E | Preclinical | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 G128V demonstrated sensitivity to treatment with VRT11E, resulting in decreased cell growth in culture (PMID: 24265153). | 24265153 | |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 |
| BRAF V600E MAP2K1 P162S | melanoma | sensitive | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited growth of BRAF V600E-mutant melanoma cells expressing MAP2K2 P162S in culture (PMID: 24265154). | 24265154 | |
| BRAF V600E MAP2K1 K57E | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of MAP2K1 K57E in a melanoma cell line harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600E MAP2K1 P124Q | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in cell culture (PMID: 25370473). | 25370473 | |
| BRAF V600E BRAF amp | 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 24 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, amplification of BRAF V600E was identified as an acquired alteration at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E BRAF amp | colorectal cancer | resistant | Cetuximab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 16 weeks to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment, amplification of BRAF V600E was identified as an acquired alteration at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E BRAF amp | colorectal cancer | resistant | Cetuximab + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to combination therapy consisting of Erbitux (cetuximab) and Zelboraf (vemurafenib) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E BRAF amp | colorectal cancer | resistant | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E that acquired BRAF V600E amplification and subsequent resistance to Erbitux (cetuximab) and Selumetinib (AZD6244) combination treatment were resistant to SCH772984 in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E BRAF amp | colorectal cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cetuximab + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E developed sustained activation of Mapk signaling and resistance to Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment in culture, likely due to the acquired BRAF V600E amplification (PMID: 27312529). | 27312529 |
| BRAF V600E BRAF amp | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + SCH772984 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable tumor inhibition in cell line xenograft models of BRAF V600E mutated lung adenocarcinoma cells that acquired resistance to Erk inhibitors through BRAF amplification (PMID: 28714990). | 28714990 |
| BRAF V600E BRAF amp | lung adenocarcinoma | decreased response | SCH772984 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived BRAF V600E mutant lung adenocarcinoma cells that acquired resistance to Erk inhibitor through BRAF amplification were less sensitive to SCH772984 in culture (PMID: 28714990). | 28714990 | |
| BRAF V600E PIK3CA H1047R | colorectal cancer | sensitive | MK2206 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with MK2206 induced apoptosis and synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 22180495). | 22180495 | |
| BRAF V600E PIK3CA H1047R | colorectal cancer | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit proliferation of colorectal cancer cells harboring BRAF V600E and PIK3CA H1047R in culture, and did not inhibit tumor growth in a cell line xenograft model (PMID: 22180495). | 22180495 | |
| BRAF V600E PIK3CA H1047R | colorectal cancer | predicted - sensitive | MK2206 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MK2206 treatment resulted in a modest tumor growth inhibition in a cell line xenograft model of colorectal cancer harboring BRAF V600E and PIK3CA H1047R (PMID: 22180495). | 22180495 | |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | resistant | Everolimus | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to treatment with Afinitor (everolimus) (PMID: 27797976). | 27797976 | |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated resistance to the combination therapy, Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 27797976). | 27797976 |
| BRAF V600E PIK3CA H1047R | thyroid gland carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Everolimus + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with anaplastic thyroid carcinoma co-harboring BRAF V600E and PIK3CA H1047R demonstrated tumor regression when treated with the triple combination, Tafinlar (dabrafenib), Mekinist (trametinib), and Afinitor (everolimus) (PMID: 27797976). | 27797976 |
| BRAF V600E PIK3CA H1047K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Miransertib + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a melanoma patient-derived xenograft (PDX) model harboring BRAF V600E and PIK3CA H1047K was sensitive to the combination treatment of Miransertib (ARQ092) and Mekinist (trametinib), demonstrating a greater inhibition of tumor growth when compared to either agent alone (PMID: 26469692). | 26469692 |
| BRAF V600E PIK3CA mut | colorectal cancer | sensitive | ASN003 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a colorectal cancer cell line xenograft model co-harboring BRAF V600E and a PIK3CA mutation demonstrated tumor growth inhibition when treated with ASN003 (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B100). | detail... | |
| BRAF V600E MAP2K1 I111N | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 I111N | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 I111N in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 E203K | melanoma | sensitive | Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, BVD-523 (ulixertinib) inhibited proliferation of melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 E203K | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 E203K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF V600E MAP2K1 P124L | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Zelboraf (vemurafenib) in culture (PMID: 28655712). | 28655712 | |
| BRAF V600E MAP2K1 P124L | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 P124L demonstrated a decreased response to treatment with Mekinist (trametinib) in culture (PMID: 28655712). | 28655712 |
| BRAF L514V BRAF V600E | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Tafinlar (dabrafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | decreased response | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to TAK-632-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | predicted - sensitive | BGB3290 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB3290 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | predicted - sensitive | BGB3245 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB3245 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | ganglioglioma | resistant | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E progressed after initial response to Tafinlar (dabrafenib) treatment, and was found to have acquired a BRAF L514V in cis with BRAF V600E, which conferred dabrafenib resistance in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | decreased response | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 | |
| BRAF L514V BRAF V600E | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). | 29880583 |
| BRAF L514V BRAF V600E | melanoma | predicted - sensitive | SCH772984 | Preclinical - Cell culture | Actionable | In a preclinical study, SCH772984 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). | 29880583 | |
| BRAF V600E MAP2K1 K57T | refractory hairy cell leukemia | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a single patient with hairy cell leukemia who relapsed after initial response to Zelboraf (vemurafenib) was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant, and demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). | 30341394 |
| BRAF V600E MAP2K1 K57T | hairy cell leukemia | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). | 30341394 | |
| BRAF V600E NRAS G13R | colorectal cancer | predicted - sensitive | BGB659 + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment resulted in sustained inhibition of Mek and Erk phosphorylation, lead to tumor regression in patient-derived xenograft models of colorectal cancer harboring BRAF V600E and NRAS G13R (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS G13R | 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, NRAS G13R was identified as an acquired mutation in liver metastasis at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS amp | 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 achieving stable disease for 16 weeks with Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS amplification was identified as an acquired alteration at the time of progression (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS over exp | colorectal cancer | resistant | Cetuximab + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, overexpression of wild-type NRAS in colorectal cancer cell lines harboring BRAF V600E induced Ras activation and Braf/Craf dimerization, conferred resistance to Erbitux (cetuximab) and Zelboraf (vemurafenib) combination treatment in culture and in cell line xenograft models (PMID: 28951457). | 28951457 | |
| BRAF V600E NRAS over exp | colorectal cancer | sensitive | BGB659 + Cetuximab | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 and Erbitux (cetuximab) combination treatment demonstrated enhanced inhibition of Erk phosphorylation and growth in BRAF V600E colorectal cancer cell lines overexpressing Nras in culture (PMID: 28951457). | 28951457 | |
| BCORL1 Q1076H BRAF V600E | melanoma | decreased response | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, expression of BCORL1 Q1076H resulted in decreased sensitivity to Zelboraf (vemurafenib) in a melanoma cell line harboring BRAF V600E in culture (PMID: 29605720). | 29605720 | |
| BRAF V600E MAP2K1 I99T | 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 I99T demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 |
| BRAF V600E MAP2K1 I99G | 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 I99G demonstrated resistance to Mekinist (trametinib) treatment in culture (PMID: 31925410). | 31925410 |
| BRAF V600E MAP2K1 I99M | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing MAP2K1 I99M demonstrated sensitivity to Mekinist (trametinib) treatment similar to cells expressing wild-type MAPK21 in culture (PMID: 31925410). | 31925410 |
| BRAF V600E STAG2 K1083* | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to inhibit colony formation and reduce Erk activation in a melanoma cell line harboring BRAF V600E that was found to have acquired a STAG2 K1083* mutation in culture (PMID: 27500726). | 27500726 | |
| BRAF V600E STAG2 D193N | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to inhibit colony formation and reduce Erk activation in a melanoma cell line harboring BRAF V600E that was found to have acquired a STAG2 D193N mutation in culture (PMID: 27500726). | 27500726 | |
| BRAF V600E BRAF V600M | melanoma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a BRAF V600E and V600M harboring malignant melanoma patient with a rapidly growing tumor burden achieved a 60% reduction in tumor size 1-week following treatment with Tafinlar (dabrafenib), and the tumor completely disappeared 1-month post-treatment (PMID: 23031422). | 23031422 | |
| BRAF V600E CDKN2A R80* | skin melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic giant sarcomatoid melanoma harboring BRAF V600E and CDKN2A R80* achieved a partial response following four months of treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and reached a complete response with regression of lung and bone metastases after one year of treatment (PMID: 32922664). | 32922664 |
| BRAF G469R NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 | |
| BRAF G469R NRAS Q61K | melanoma | sensitive | LY3009120 | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| BRAF G469R NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| BRAF V600R | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF 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 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 L505H | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). | 24283590 | |
| BRAF L597R | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597R with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 | |
| BRAF L597R | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). | 22798288 |
| BRAF N581Y | colon cancer | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, colon cancer cells harboring BRAF N581Y were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). | 19276360 | |
| BRAF V600M | 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 5.9 months in the patient harboring BRAF V600M (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF N581D | lung non-small cell carcinoma | predicted - sensitive | RMC-4550 | Preclinical - Pdx | Actionable | In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF D594N (PMID: 30104724). | 30104724 | |
| BRAF 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 | 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 | gastrointestinal system cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 4 patients with gastrointestinal system cancer harboring BRAF D594G (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF D594G | lung adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF D594G (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF D594G NRAS G12D | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring both BRAF D594G and NRAS G12D demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring both BRAF D594G and NRAS G12D in culture (PMID: 27523909). | 27523909 | |
| BRAF D594G NRAS G12D | melanoma | decreased response | 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 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 | 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 | 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 | 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 | 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 | thyroid gland cancer | sensitive | CLM3 | Preclinical | Actionable | In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression, in BRAF wild-type thyroid cancer cells in culture (PMID: 24423321). | 24423321 | |
| BRAF wild-type | melanoma | 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 | 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 | 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 | 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 | 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 | malignant 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 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 | 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 | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). | 27523909 | |
| BRAF wild-type NRAS wild-type | melanoma | resistant | 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 | 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 | 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 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 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 wild-type ERBB2 amp NRAS wild-type | colon cancer | sensitive | Pertuzumab + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BRAF wild-type (NCCN.org). | detail... | |
| BRAF wild-type ERBB2 amp NRAS wild-type | colon cancer | sensitive | Lapatinib + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BBRAF wild-type (NCCN.org). | detail... | |
| BRAF wild-type ERBB2 amp NRAS wild-type | rectum cancer | sensitive | Lapatinib + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). | detail... | |
| BRAF wild-type ERBB2 amp NRAS wild-type | rectum cancer | sensitive | Pertuzumab + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). | detail... | |
| 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 | 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 | 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 | 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 | 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 G469A | lung adenocarcinoma | sensitive | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G469A in culture, and reduced tumor growth in xenograft models (PMID: 27834212). | 27834212 | |
| BRAF G469A | 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 G469A, who remained on therapy for 20.4 months without progression (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G469A | lung non-small cell carcinoma | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a non-small lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 | |
| BRAF G469A | head and neck cancer | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021). | 29247021 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | TAE226 | Preclinical | Actionable | In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring BRAF G469A mutation in culture (PMID: 26090892). | 26090892 | |
| BRAF G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G469A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring BRAF G469A demonstrated resistance to induction of apoptosis by Zelboraf (vemurafenib,) and treatment with Zelboraf (vemurafenib) was not effective in inhibiting growth in culture (PMID: 25706985). | 25706985 | |
| BRAF G469A | lung cancer | resistant | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of lung cancer cells harboring BRAF G469A in culture (PMID: 30104724). | 30104724 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) induced apoptosis and inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 25706985). | 25706985 |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased viability and enhanced ERK inhibition compared to either agent alone, in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 28947956). | 28947956 |
| BRAF G469A | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469A (PMID: 26343582). | 26343582 | |
| BRAF G469A | 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, 2 of the non-responding patients harbored BRAF G469A (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF G469A | lung non-small cell carcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture, and prevented Mekinist (trametinib)-related activation of AKT and resulted in increased induction of apoptosis compared to either agent alone (PMID: 25706985). | 25706985 |
| BRAF G469A | lung non-small cell carcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 |
| BRAF G469A | small intestine carcinoma | sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021). | 29247021 | |
| BRAF V487_P492delinsA | pancreatic cancer | sensitive | LY3009120 | LY3009120 | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA were sensitive to LY3009120 in culture and in xenograft models, resulting in inhibition of tumor growth and partial tumor regression (PMID: 26732095). | 26732095 |
| BRAF V487_P492delinsA | pancreatic cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). | 26732095 |
| BRAF V487_P492delinsA | pancreatic cancer | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Tafinlar (dabrafenib) (PMID: 26732095). | 26732095 | |
| BRAF V487_P492delinsA | pancreatic cancer | resistant | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). | 26732095 | |
| BRAF Y472C | lung non-small cell carcinoma | sensitive | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sprycel (dasatinib) induced apoptosis in non-small cell lung carcinoma cells harboring BRAF Y472C in culture (PMID: 22649091). | 22649091 | |
| BRAF L485S | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells expressing BRAF L485S demonstrated resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). | 31925410 | |
| 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) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and V600K are on the companion diagnostic. | 29573941 detail... detail... detail... |
| BRAF V600E/K | melanoma | sensitive | 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 | 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 | 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 | 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 | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF V600E/K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292; NCT00687622). | 22805292 |
| BRAF V600E/K | 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 | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | The combination of Tafinlar (dabrafenib) and Mekinist (trametinib) is included in guidelines as first or second-line therapy in patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation (PMID: 30715168, PMID: 30285222; ESMO.org). | 30715168 30285222 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 | 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 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 | 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 |