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| Profile Name | BRAF D594Y |
| Gene Variant Detail | |
| Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | pancreatic adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | Advanced Solid Tumor | no benefit | 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 | 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 | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF non-V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). | 30268448 | |
| BRAF mutant | lung non-small cell carcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study | Actionable | In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). | 31367539 | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring a BRAF mutation in culture (PMID: 27307593). | 27307593 |
| BRAF mutant | melanoma | 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 | 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 | 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 | 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 | colorectal cancer | sensitive | MLN2480 | Preclinical | Actionable | In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). | detail... | |
| BRAF mutant | Advanced Solid Tumor | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, cancer cell lines harboring BRAF mutations demonstrated increased sensitivity to RAF709 compared to BRAF wild-type cells in culture (PMID: 29343524). | 29343524 | |
| BRAF mutant | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| BRAF mutant | melanoma | sensitive | Vemurafenib + Voruciclib | Phase I | Actionable | In a Phase I trial, Voruciclib (P1446A-05) and Zelboraf (vemurafenib) combination therapy demonstrated safety and preliminary efficacy, resulted in complete response in 33% (1/3) and partial response in 67% (2/3) of BRAFi-naïve melanoma patients harboring BRAF mutations (J Clin Oncol 33, 2015 (suppl; abstr 9076)). | detail... | |
| BRAF mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... | |
| BRAF mutant | 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 | 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 | 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 | 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 | 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 | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). | 22460902 | |
| BRAF mutant | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation of several melanoma cell lines in culture and hypersensitivity was associated with BRAF mutations (PMID: 23039341). | 23039341 |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + Encorafenib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination therapy of Erbitux (cetuximab) and Encorafenib (LGX818) in colorectal cancer patients harboring a BRAF mutation resulted in an overall response rate of 19% (5/26), including 1 patient with a complete response and 4 patients with a partial response, and led to a median progression free survival of 3.7 months and response duration of 46 weeks (PMID: 28363909). | 28363909 | |
| BRAF mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (AJ Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... | |
| BRAF mutant | lung 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 | 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 | 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 | colon cancer | predicted - sensitive | PF-00477736 + PF3644022 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited tumor growth in cell line xenograft models of BRAF mutant colon cancer (PMID: 26140595). | 26140595 | |
| BRAF mutant | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) synergistically inhibited tumor growth in patient-derived xenograft models of colorectal cancer harboring BRAF mutations, resulted in a disease control rate of 41.7% (5/12) (PMID: 28611205). | 28611205 | |
| BRAF mutant | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 treatment resulted in tumor regression in BRAF mutant-melanoma cell line xenograft models (PMID: 28775144). | 28775144 | |
| BRAF mutant | melanoma | predicted - sensitive | 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 | 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 | Selumetinib | Case Reports/Case Series | Actionable | In a Phase II trial, 5 out of 6 patients with advanced melanoma exhibiting a response to Koselugo (selumetinib) had BRAF-mutant tumors (PMID: 22048237). | 22048237 |
| BRAF mutant | colorectal cancer | decreased response | PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, BRAF mutant colorectal cancer cell lines demonstrated reduced sensitivity to PLX4720 in culture (PMID: 26351322). | 26351322 | |
| BRAF mutant | colorectal cancer | 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 adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). | 26343583 |
| BRAF mutant | melanoma | 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 | 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 | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 | |
| BRAF mutant | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Phase II | Actionable | In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring BRAF non-V600E mutations, resulting in an objective response rate of 12.5% (1/8), BRAF mutations including class 1 (n=1), class 2 (n=3), and class 3 (n=5) (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). | detail... |
| BRAF mutant | lung non-small cell carcinoma | predicted - sensitive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... | |
| BRAF mutant | 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 | 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 | 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 mut TP53 wild-type | melanoma | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). | 25567130 | |
| BRAF mut TP53 wild-type | colorectal cancer | sensitive | CGM097 + Dabrafenib + Navitoclax + PF-04217903 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 | |
| BRAF mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + SAR405838 | Phase I | Actionable | In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). | 30585255 |
| BRAF mut TP53 wild-type | melanoma | sensitive | CGM097 + Encorafenib | Preclinical | Actionable | In a preclinical study, the combination of CGM097 and Encorafenib (LGX818) synergized to inhibit cell growth of a human melanoma cell line harboring mutant BRAF and wild-type TP53 in culture, and promoted tumor regression in xenograft models (Cancer Res October 1, 2014 74; 5466). | detail... | |
| BRAF mut NRAS mut | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 50% (1/2) of melanoma patients harboring both BRAF and NRAS mutations (PMID: 26169970). | 26169970 | |
| BRAF mut NRAS mut | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BI-847325 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with BI-847325 inhibited growth of a BRAF-mutant melanoma cell line with BRAF-inhibitor resistance due to an NRAS mutation in culture (PMID: 25873592). | 25873592 |
| BRAF mut NRAS wild-type | melanoma | sensitive | Lenvatinib | Phase I | Actionable | In a Phase I clinical trial, Lenvima (lenvatinib) treatment resulted in stable disease in 100% (5/5) of melanoma patients harboring BRAF mutations and wild-type NRAS (PMID: 26169970). | 26169970 | |
| BRAF mut PTEN loss | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | SAR260301 + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Selumetinib (AZD6244) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | no benefit | GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 | |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 | |
| BRAF mut PTEN loss | melanoma | sensitive | GSK2636771 + Pembrolizumab | Preclinical | Actionable | In a preclinical study, a melanoma mouse model harboring a BRAF mutation and PTEN loss was sensitive to the combination of GSK2636771 and Keytruda (pembrolizumab), demonstrating greater tumor growth inhibition and improved survival when compared to either therapy alone (PMID: 26645196). | 26645196 | |
| BRAF mut PTEN loss | melanoma | no benefit | Pembrolizumab | Preclinical | Actionable | In a preclinical study, Keytruda (pembrolizumab) resulted in no benefit in a melanoma mouse model co-harboring a BRAF mutation and PTEN loss (PMID: 26645196). | 26645196 | |
| BRAF mut PTEN loss | melanoma | sensitive | SAR260301 + Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 and Zelboraf (vemurafenib) synergistically inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 | |
| BRAF mut PTEN mut | melanoma | decreased response | MEK1 Inhibitor | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytostatic response in melanoma cell lines harboring both BRAF and PTEN mutations in culture and only inhibited tumor growth at very high doses in cell line xenograft models (PMID: 23039341). | 23039341 |
| BRAF mut PTEN mut | melanoma | predicted - sensitive | ST-162 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ST-162 resulted in tumor regression in a melanoma cell line xenograft model co-harboring mutations in BRAF and PTEN (PMID: 28775144). | 28775144 | |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, AZD6482 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN wild-type | melanoma | no benefit | Encorafenib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN wild-type | melanoma | no benefit | GSK2636771 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, AZD6482 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN wild-type | melanoma | sensitive | MEK1 Inhibitor | E6201 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, E6201 resulted in a cytocidal response in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture and inhibited tumor growth in cell line xenograft models (PMID: 23039341). | 23039341 |
| BRAF mut PTEN wild-type | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD6482 + Binimetinib | Preclinical | Actionable | In a preclinical study, AZD6482 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Pictilisib | Preclinical | Actionable | In a preclincal study, Pictilisib (GDC-0941) inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Alpelisib + AZD6482 + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | TGX-221 | Preclinical | Actionable | In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 and Alpelisib (BYL719) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | GSK2636771 + unspecified IGF-1R antibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | GSK2636771 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, GSK2636771 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Alpelisib + AZD6482 + Binimetinib + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + Encorafenib + GSK2636771 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of GSK2636771, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently inhibited tumor growth in xenograft models of a human melanoma cell line harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + unspecified IGF-1R antibody | Preclinical | Actionable | In a preclinical study, combination treatment consists of Encorafenib (LGX818) and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD6482 + Binimetinib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 | Preclinical | Actionable | In a preclincal study, AZD6482 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD6482 + Binimetinib | Preclinical | Actionable | In a preclinical study, AZD6482 and Binimetinib (MEK162) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, AZD6482 and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | NVP-AEW541 + Pictilisib | Preclinical | Actionable | In a preclinical study, Pictilisib (GDC-0941) and NVP-AEW541 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Encorafenib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | no benefit | Alpelisib + Encorafenib | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and Encorafenib (LGX818) combination treatment did not enhance growth inhibition in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + GSK2636771 + unspecified IGF-1R antibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment consisting of GSK2636771, Encorafenib (LGX818), and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Encorafenib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Alpelisib + Binimetinib | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | no benefit | Alpelisib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, Alpelisib (BYL719) and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, AZD6482 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | decreased response | Alpelisib | Preclinical | Actionable | In a preclincal study, melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations were less sensitive to Alpelisib (BYL719)-induced growth inhibition in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + GSK2636771 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of GSK2636771 and Alpelisib (BYL719) synergized to inhibit proliferation of human melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture, and inhibited tumor growth in xenograft models of one cell line harboring these mutations (PMID: 26577700). | 26577700 | |
| BRAF mut PTEN inact mut | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | AZD6482 + Binimetinib + Encorafenib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PDGFRB over exp | 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 PDGFRB over expression in culture (PMID: 25873592). | 25873592 |
| 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 RB1 loss | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| BRAF mut TP53 mut | colorectal cancer | sensitive | Alpelisib + Dabrafenib + Erlotinib + Navitoclax | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 | |
| BRAF mut PIK3CA wild-type | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | TAK-733 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, mutations in BRAF, KRAS, or NRAS were associated with sensitivity to TAK-733 in colorectal cancer cell lines in culture, and patient-derived xenograft models harboring KRAS or BRAF mutations with wild-type PIK3CA demonstrated a trend toward higher tumor growth inhibition following TAK-733 treatment (PMID: 26439693). | 26439693 |
| BRAF mut IDH1 wild-type | glioblastoma | predicted - sensitive | 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 mut IDH1 wild-type | glioblastoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, MAPK pathway mutations were significantly enriched in patients with IDH1 wild-type glioblastoma who responded to anti-PD-1 therapy with either Keytruda (pembrolizumab) or Opdivo (nivolumab), compared to those who did not respond (odds ratio=12.8, p=0.019), with 4 MAPK pathway mutations (2 in BRAF, 2 in PTPN11) identified in 13 responders and 1 (BRAF) in 32 non-responders (PMID: 30742119). | 30742119 | |
| BRAF 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 | predicted - sensitive | Nivolumab | Phase III | Actionable | In a Phase III trial (CheckMate-066), Opdivo (nivolumab) treatment resulted in improved overall survival and response compared to treatment with Deticene (dacarbazine) in melanoma patients with wild-type BRAF, including a 3-year overall survival (OS) rate of 51.2% vs. 21.6%, a median OS of 37.5 months vs. 11.2 months, a complete response in 19% (40/210) vs. 1.4% (3/208), and a partial response in 23.8% (50/210) vs. 13% (27/208), respectively (PMID: 30422243; NCT01721772). | 30422243 | |
| BRAF wild-type | Advanced Solid Tumor | resistant | BGB-283 | Preclinical - Cell culture | Actionable | In a preclinical study, a variety of BRAF wild-type tumor cell lines were insensitive to BGB-283 in culture (PMID: 26208524). | 26208524 | |
| BRAF wild-type | melanoma | 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 | rectum cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vectibix (panitumumab) is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| BRAF wild-type | melanoma | no benefit | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 | |
| BRAF wild-type | melanoma | 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 | high grade glioma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and Selumetinib (AZD6244) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 |
| BRAF wild-type | melanoma | 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 | no benefit | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 | |
| BRAF wild-type | rectum cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic rectal cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| BRAF wild-type | melanoma | 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 | colon cancer | predicted - sensitive | Panitumumab | Guideline | Actionable | Vectibix (panitumumab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| BRAF wild-type | colon cancer | predicted - sensitive | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), alone and in combination with chemotherapy, is included in guidelines for patients with advanced or metastatic colon cancer that is BRAF wild-type, KRAS wild-type, and NRAS wild-type (NCCN.org). | detail... | |
| BRAF wild-type | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Phase II | Actionable | In a Phase II trial, a favorable response rate to Koselugo (selumetinib) was observed in BRAF-mutant, but not BRAF wild-type, melanoma patients (PMID: 22048237). | 22048237 |
| BRAF wild-type | melanoma | predicted - sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived wild-type BRAF melanoma cells in culture (PMID: 23715574). | 23715574 | |
| BRAF wild-type | lung non-small cell carcinoma | resistant | GDC0879 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type non-small cell lung cancer cells in culture and in patient-derived xenograft models (PMID: 19276360). | 19276360 | |
| BRAF wild-type | 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 | 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 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 | 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 | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of BRAF and NRAS wild-type melanoma cells in culture (PMID: 27523909). | 27523909 | |
| BRAF wild-type NRAS wild-type | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line with wild-type BRAF and wild-type NRAS in culture (PMID: 27307593). | 27307593 |
| BRAF wild-type NRAS wild-type | melanoma | resistant | 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 | 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 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 V600X | 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 as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Tafinlar (dabrafenib) plus Mekinist (trametinib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | melanoma | sensitive | MK2206 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of MK2206 and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 | |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II clinical trial, patients with BRAF V600 mutant melanoma (n=78) treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) had a median overall survival of greater than 2 years (PMID: 26811525). | 26811525 |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Selumetinib (AZD6244) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | skin melanoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... | |
| BRAF V600X | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Spartalizumab + Trametinib | Phase III | Actionable | In a Phase III trial (COMBI-i), the combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Spartalizumab (PDR001) resulted in an objective response rate of 78% (28/36, 16 complete, 12 partial), disease control rate of 94% (34/36), and median progression-free survival of 23 months in patients with BRAF V600-mutant metastatic melanoma, including 29 patients (81%) harboring BRAF V600E and 4 patients (11%) harboring BRAF V600K (PMID: 33020648; NCT02967692). | 33020648 |
| BRAF V600X | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib + Pembrolizumab | Phase I | Actionable | In a Phase I trial (IMMU-Target), Mektovi (binimetinib), Braftovi (encorafenib), and Keytruda (pembrolizumab) demonstrated safety and preliminary efficacy in treatment naive patients with advanced melanoma harboring BRAF V600 mutations, resulting in an overall response rate of 64% (9/14), with a 12-month progression-free survival rate of 37.5% (n=8) and 60% (n=6) at the two tested dose levels, respectively (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9532; NCT02902042). | detail... |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Buparlisib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | low grade glioma | predicted - sensitive | Dabrafenib | Phase Ib/II | Actionable | In a Phase I/II trial, Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in an objective response rate of 44% (14/32, 1 complete response, 13 partial response) and a disease control rate of 78% (25/32), with a median duration of response of 26 months in pediatric patients with BRAF V600-mutant low-grade gliomas (PMID: 31811016; NCT01677741). | 31811016 | |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | BGB-283 | Phase I | Actionable | In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 5 patients with BRAF V600E/K-mutant melanoma, 2 patients with BRAF V600E-mutant thyroid cancer, and 1 patient with BRAF V600E-mutant low-grade serous ovarian carcinoma, complete response in 1.9% (1/53), in a patient with melanoma, and stable disease in 50.9% (27/53) (PMID: 32182156; NCT02610361). | 32182156 | |
| BRAF V600X | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF V600X | cholangiocarcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in partial response in 12% (1/8) and stable disease in 50% (4/8) of cholangiocarcinoma patients with BRAF V600 mutations (PMID: 26287849). | 26287849 | |
| BRAF V600X | ganglioglioma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Tafinlar (dabrafenib) treatment resulted in a partial response in a pediatric patient with BRAF V600-mutant ganglioglioma (PMID: 31811016; NCT01677741). | 31811016 | |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib + Vemurafenib | Guideline | Actionable | Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) combination therapy is included in guidelines as a preferred first-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) therapy is included in guidelines for patients with unresectable or metastatic cutaneous melanoma harboring BRAF V600 activating mutations, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). | detail... | |
| BRAF V600X | melanoma | sensitive | Buparlisib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 | |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Guideline | Actionable | Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Mektovi (binimetinib) plus Braftovi (encorafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | thyroid gland cancer | predicted - sensitive | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) resulted in an overall response rate of 29% (2/7), with 1 complete response and 1 partial response, in patients with anaplastic thyroid cancer patients with BRAF V600 mutations (PMID: 26287849). | 26287849 | |
| BRAF V600X | 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-line therapy for patients with metastatic non-small cell lung cancer harboring a BRAF V600 mutation, or as subsequent therapy in patients harboring BRAF V600 mutations that have not received prior BRAF/MEK inhibitor therapy (PMID: 32169226; ESMO.org). | 32169226 detail... |
| BRAF V600X | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) resulted in an overall response rate of 4% (1/26), stable disease in 69% (18/26), and a median progression-free survival of 3.7 months in patients with BRAF V600-mutant colorectal cancer (PMID: 26287849). | 26287849 | |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Buparlisib + Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Buparlisib (BKM120) and Koselugo (selumetinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | BRAF inhibitor plus MEK inhibitor combination therapy, such as Cotellic (cobimetinib) plus Zelboraf (vemurafenib), is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring a BRAF V600 mutation (PMID: 31566661; ESMO.org). | 31566661 detail... |
| BRAF V600X | skin melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as a second-line or subsequent therapy for patients with metastatic or unresectable cutaneous melanoma harboring a BRAF V600 activating mutation (NCCN.org). | detail... |
| BRAF V600X | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II trial, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in partial response or better in 12% (5/43), including 1 complete response, and stable disease in 51% (22/43) of patients with BRAF V600-mutant colorectal cancer (PMID: 26392102). | detail... 26392102 |
| BRAF V600X | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Nivolumab + Trametinib | Phase II | Actionable | In a Phase II trial, combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Opdivo (nivolumab) resulted in an objective response rate (ORR) of 92% (24/27, 3 CR, 21 PR) in patients with MEK inhibitor-naive, BRAF V600-mutated melanoma, with a median progression-free survival of 8.5 mos, ORR was 88% (14/16) and 100% (10/10) in PD1 refractory or naive patients, 57% (4/7) of patients with brain metastasis achieved intracranial response (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 9520; NCT02910700). | detail... |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | MK2206 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of MK2206 and Mekinist (trametinib) inhibited growth of BRAF V600-mutant melanoma cell lines in culture, with increased efficacy over either agent alone (PMID: 24265152). | 24265152 |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | Dabrafenib | Phase I | Actionable | In a Phase I trial (BRF116013), Tafinlar (dabrafenib) treatment was well tolerated and demonstrated preliminary efficacy, resulted in a median duration of treatment of 75.6 week in pediatric patients with BRAF V600-mutant advanced solid tumors, including low-grade (n=15) and high-grade (n=8) gliomas, Langerhans cell histiocytosis (n=2), neuroblastoma (n=1), and papillary thyroid cancer (n=1) (PMID: 31506385; NCT01677741). | 31506385 | |
| BRAF V600X | colorectal cancer | no benefit | Vemurafenib | Phase II | Actionable | In a Phase II clinical trial, treatment with Zelboraf (vemurafenib) in colorectal cancer patients with BRAF V600 mutations did not result in clinical benefit, with no patients achieving response, and 50% (5/10) demonstrating progressive disease (PMID: 26287849). | 26287849 | |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in a partial response in 20% (8/41) of melanoma patients harboring BRAF V600 mutations, including V600E (33/41), V600K (5/41), and V600R (1/41) (PMID: 23414587; NCT01320085). | 23414587 |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Phase III | Actionable | In a Phase III trial, combination treatment with Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months compared to 7.2 months with Zelboraf (vemurafenib) alone among patients with BRAF V600-mutated metastatic melanoma (PMID: 27480103; NCT01689519). | 27480103 |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib + Vemurafenib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab), Zelboraf (vemurafenib), and Cotellic (cobimetinib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 71.8% (28/39), with a complete response in 20.5% (8/39), a median progression-free survival of 12.9 months, a median overall survival not yet reached, and median duration of confirmed response of 17.4 months (PMID: 31171876; NCT01656642). | detail... 31171876 |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Atezolizumab + Cobimetinib + Vemurafenib | FDA approved | Actionable | In a Phase III trial (IMspire150) that supported FDA approval, addition of Tecentriq (atezolizumab) to Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy significantly improved progression-free survival (15.1 vs 10.6 months, HR=0.78, p=0.025) compared to control in patients with advanced or metastatic melanoma harboring BRAF V600 mutations (PMID: 32534646; NCT02908672). | 32534646 detail... |
| BRAF V600X | melanoma | sensitive | ASN003 | Preclinical - Pdx | Actionable | In a preclinical study, melanoma patient derived xenograft (PDX) model harboring a BRAF V600 mutation demonstrated antitumor activity when treated with ASN003 (J Clin Oncol 35, 2017 (suppl; abstr e14102)). | detail... | |
| BRAF V600X | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + KRT-232 + Trametinib | Phase I | Actionable | In a Phase I trial, the combination therapy of KRT-232 (AMG 232), Mekinist (trametinib), and Tafinlar (dabrafenib) in 6 patients with metastatic cutaneous melanoma harboring a BRAF V600 mutation resulted in 4 patients with a partial response and 2 patients with stable disease, and of the 6 patients, all experienced tumor reduction (J Clin Oncol 35, 2017 (suppl; abstr 2575)). | detail... |
| BRAF V600X | melanoma | sensitive | Atezolizumab + Vemurafenib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination therapy of Tecentriq (atezolizumab) and Zelboraf (vemurafenib) in patients with metastatic melanoma harboring a BRAF V600 mutation resulted in a best objective response rate of 76.5% (13/17), with a complete response in 17.6% (3/17), a median progression-free survival of 10.9 months, a median overall survival of 46.2 months, and median duration of confirmed response of 10.6 months (PMID: 31171876; NCT01656642). | 31171876 | |
| BRAF V600X | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Belvarafenib + Cobimetinib | Phase I | Actionable | In a Phase Ib trial, combination treatment with Belvarafenib (HM95573) and Cotellic (cobimetinib) was well-tolerated and demonstrated safety, and led to a confirmed partial response in 33.3% (3/9) solid tumor patients harboring BRAF V600 mutations (Annals of Oncology 32 (2021): S595; NCT03839342). | detail... |
| BRAF V600X PIK3CA H1047X | ovarian carcinoma | predicted - sensitive | Bevacizumab + Pegylated liposomal-doxorubicin + Temsirolimus | Case Reports/Case Series | Actionable | In a clinical study, the combination of Torisel (temsirolimus) plus Avastin (bevacizumab) and Doxil (pegylated liposomal-doxorubicin) resulted in a partial response in a patient with ovarian clear cell carcinoma harboring PIK3CA H1047 and BRAF V600 mutations (PMID: 21216929). | 21216929 | |
| BRAF V600X MAP2K1 V60E NRAS T58I NRAS Q61R | melanoma | predicted - resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistance-associated mutations, MAP2K1 V60E, NRAS T58I, and NRAS Q61R, after 18 weeks of treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 | |
| BRAF V600X BRAF amp NRAS Q61K | melanoma | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 | |
| BRAF V600X PTEN H93D | melanoma | predicted - sensitive | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation and PTEN H93D treated with Zelboraf (vemurafenib) for 66 weeks demonstrated a partial response (PMID: 24265153). | 24265153 | |
| BRAF V600X PTEN neg | melanoma | sensitive | Uprosertib | Preclinical - Cell culture | Actionable | In a preclinical study, lack of PTEN expression was associated with increased sensitivity to GSK2141795 in BRAF V600-mutant melanoma cell lines in culture (PMID: 24265152). | 24265152 | |
| BRAF 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 | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600R in culture (PMID: 27523909). | 27523909 | |
| BRAF V600R | melanoma | sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600R treated with Tafinlar (dabrafenib) demonstrated a reduction in lesion size after 2.5 months and at 5 months, stable disease, however, after 7 months progression ensued (PMID: 27255157). | 27255157 | |
| BRAF 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 K601N | lung non-small cell carcinoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 2 patients harboring BRAF K601N, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF K601N | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF K601N (PMID: 26343582). | 26343582 | |
| BRAF K601N | chronic lymphocytic leukemia | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of chronic lymphocytic leukemia cells harboring BRAF K601N in culture (PMID: 30559419). | 30559419 | |
| BRAF K601N | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF K601N achieving an unconfirmed PR (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... | |
| BRAF K601N | hematologic cancer | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, a hematological tumor cell line harboring BRAF K601N demonstrated sensitivity to LY3009120 in culture (PMID: 26732095). | 26732095 | |
| BRAF G466E | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | melanoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF G466E | 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 | 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 | 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 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 L597K | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) resulted in a partial response and clinical improvement in a patient with metastatic melanoma harboring BRAF L597K (PMID: 33560788). | 33560788 |
| BRAF G464E | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464E (PMID: 26343582). | 26343582 | |
| BRAF G464E | sarcomatoid carcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 6.9 months in a patient with spindle cell carcinoma harboring a BRAF G464E (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF S365L BRAF V600E | lung papillary adenocarcinoma | predicted - sensitive | Bevacizumab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) and Avastin (bevacizumab) combination treatment resulted in regression of some brain lesions while others remained stable in a patient with lung papillary carcinoma harboring BRAF V600E and S365L (PMID: 34178685). | 34178685 | |
| BRAF S365L BRAF V600E | lung papillary adenocarcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung papillary carcinoma harboring BRAF V600E who previously responded to Tafinlar (dabrafenib) and Mekinist (trametinib) treatment was found to have acquired BRAF S365L upon disease progression (PMID: 34178685). | 34178685 |
| BRAF class 2 | pancreatic cancer | predicted - sensitive | KIN-2787 | Preclinical - Cell culture | Actionable | In a preclinical study, KIN-2787 treatment led to inhibition of tumor growth in a pancreatic cell line xenograft model harboring a BRAF class 2 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). | detail... | |
| BRAF N486_P490del BRAF R509H | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del BRAF R509H | Advanced Solid Tumor | sensitive | GDC0879 | Preclinical - Biochemical | Actionable | In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del BRAF R509H BRAF V600E | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del BRAF R509H BRAF V600E | Advanced Solid Tumor | sensitive | GDC0879 | Preclinical - Biochemical | Actionable | In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF R509H BRAF V600E | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical - Biochemical | Actionable | In a preclinical study, Zelboraf (vemurafenib) reduced Mek phosphorylation in transformed cells expressing BRAF V600E and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF R509H BRAF V600E | Advanced Solid Tumor | sensitive | GDC0879 | Preclinical - Biochemical | Actionable | In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF V600E and R509H in culture (PMID: 26996308). | 26996308 | |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was resistant to Tafinlar (dabrafenib) (PMID: 26732095). | 26732095 | |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to LY3009120 in both culture and xenograft models, resulting in significant tumor regression and inhibition of MEK and ERK phosphorylation (PMID: 26732095). | 26732095 | |
| BRAF L485_P490delinsY | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to Mekinist (trametinib), resulting in cell growth inhibition (PMID: 26732095). | 26732095 |
| BRAF amp | lung non-small cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study | Actionable | In a retrospective clinical study, no significant difference in overall survival (19.0 vs 18.4 months) was found in patients with non-small cell lung cancer harboring BRAF V600E (n=14), amplification (n=5), or non-V600E mutations (n=12) who received immunotherapy compared to those who never received immunotherapy (PMID: 31367539). | 31367539 | |
| BRAF V600E BRAF amp | colorectal cancer | resistant | 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 | 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 | 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 | lung adenocarcinoma | decreased response | SCH772984 | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived BRAF V600E mutant lung adenocarcinoma cells that acquired resistance to Erk inhibitor through BRAF amplification were less sensitive to SCH772984 in culture (PMID: 28714990). | 28714990 | |
| BRAF V600E BRAF amp | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + SCH772984 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination of Tafinlar (dabrafenib), SCH772984, and Mekinist (trametinib) resulted in durable tumor inhibition in cell line xenograft models of BRAF V600E mutated lung adenocarcinoma cells that acquired resistance to Erk inhibitors through BRAF amplification (PMID: 28714990). | 28714990 |
| BRAF V600E BRAF amp | colorectal cancer | 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 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 | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF G464V | 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 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 G596V | lung non-small cell carcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring BRAF G596V demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26200454). | 26200454 | |
| BRAF G596V NRAS G13R | colorectal cancer | sensitive | Cetuximab + LSN3074753 | Preclinical - Pdx | Actionable | In a preclinical study, LSN3074753 and Erbitux (cetuximab) worked synergistically, resulting in tumor regression in a patient-derived xenograft model of colorectal cancer harboring BRAF G596V and NRAS G13R (PMID: 28611205). | 28611205 | |
| BRAF L597R | prostate cancer | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of prostate cancer cells harboring BRAF L597R in culture (PMID: 30559419). | 30559419 | |
| BRAF L597R | melanoma | predicted - sensitive | Sorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment inhibited viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). | 23715574 | |
| BRAF L597R | lung adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring BRAF L597R demonstrated clinical improvement and a tumor response at 13 weeks with resolution of hepatic metastasis and mediastinal lymphadenopathy when treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib), and at the 12 month follow up remained on treatment, showing no disease progression (PMID: 32540409). | 32540409 |
| BRAF L597R | melanoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment inhibited growth of skin and lung nodules by 30% and resulted in a duration of response of over 4 months in a melanoma patient harboring BRAF L597R, and inhibited Erk activation and reduced viability of melanoma cells derived from the patient in culture (PMID: 23715574). | 23715574 | |
| BRAF L597R | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597R (PMID: 22798288). | 22798288 |
| BRAF L597R | melanoma | predicted - sensitive | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment inhibited Erk activation and reduced viability of patient-derived melanoma cells harboring BRAF L597R in culture (PMID: 23715574). | 23715574 | |
| BRAF L597R | 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 G469E | breast ductal carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, only 1 patient with breast ductal carcinoma harboring BRAF G469E achieved a partial response with a tumor shrinkage of 50% at 4 months, but the patient died suddenly at 4.3 months with no disease progression (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G469E | melanoma | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF G469E demonstrated resistance to U0126 treatment in culture (PMID: 18794803). | 18794803 |
| BRAF G469E | melanoma | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment induced apoptosis and mitochondrial depolarization, and inhibited growth of melanoma cells harboring BRAF G469E in culture (PMID: 18794803). | 18794803 | |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). | 20538618 |
| BRAF T529N BRAF V600E | Advanced Solid Tumor | conflicting | 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 | 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 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 G596D | breast cancer | predicted - resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not inhibit Erk phosphorylation in breast cancer cells expressing BRAF G596D in culture (PMID: 31158244). | 31158244 | |
| BRAF L505H | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cells expressing BRAF L505H were resistant to Zelboraf (vemurafenib) (PMID: 24283590). | 24283590 | |
| BRAF L505H BRAF V600E | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF V600E treated with Zelboraf (vemurafenib) subsequently demonstrated resistance likely due to the secondary resistance mutation, BRAF L505H (PMID: 25515853). | 25515853 | |
| BRAF E451K | breast cancer | predicted - resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment resulted in increased Erk phosphorylation in breast cancer cells expressing BRAF E451K in culture (PMID: 31158244). | 31158244 | |
| BRAF T119S BRAF V600E | colorectal cancer | predicted - sensitive | LY3214996 | Preclinical - Cell culture | Actionable | In a preclinical study, a colorectal cancer cell line harboring BRAF V600E and BRAF T119S was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell proliferation (PMID: 31744895). | 31744895 | |
| BRAF T119S BRAF V600E | colorectal cancer | predicted - resistant | BI-3406 | Preclinical - Cell culture | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of colorectal cancer cells harboring BRAF V600E and BRAF T119S in culture (PMID: 32816843). | 32816843 | |
| BRAF L597V | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF L597V | lung adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | LY3214996 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with LY3214996 in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF L597V | lung adenocarcinoma | sensitive | BGB-283 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to treatment with Lifirafenib (BGB-283) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | Encorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Braftovi (encorafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Tafinlar (dabrafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | Ravoxertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | endometrial adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease with a progression-free survival of 7.9 months in a patient with endometrial adenocarcinoma harboring BRAF L597V (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF L597V | lung adenocarcinoma | resistant | MLN2480 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with MLN2480 (TAK-580) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | lung adenocarcinoma | resistant | MK-8353 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with MK-8353 in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V | 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 L597V (PMID: 26343582). | 26343582 | |
| BRAF L597V | lung adenocarcinoma | resistant | Ulixertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ulixertinib (BVD-523) in culture (PMID: 32540409). | 32540409 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 | |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 | |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
| BRAF S363F BRAF K601E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 + 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 | 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 | 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 L597S | melanoma | sensitive | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 | |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | TAK-733 | Phase I | Actionable | In a Phase I trial, one metastatic melanoma patient carrying a BRAF L597S mutation, had a partial response to the MEK inhibitor, TAK-733 (PMID: 22798288). | 22798288 |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 89% (17/19) of tumors in a patient-derived xenograft (PDX) model harboring BRAF L597S, and treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a objective response with 34% tumor shrinkage in the patient from which the PDX model was derived from (PMID: 29903896). | 29903896 |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
| BRAF L597S | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 inhibited growth of melanoma cells harboring BRAF L597S in culture (PMID: 29903896). | 29903896 | |
| BRAF L597S | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | Preclinical studies demonstrated the MEK inhibitor, Mekinist (trametinib) caused decreased activation of MEK and ERK in cells expressing BRAF L597S (PMID: 22798288). | 22798288 |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
| BRAF L597S | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF L597S in culture, and resulted in tumor shrinkage in 75% (8/12) subcutaneous tumors in one patient-derived xenograft (PDX) model harboring BRAF L597S that also harbored a BRAF variant of unknown significance, BRAF R239Q, however, was not sufficient to induce tumor shrinkage in a second PDX model with BRAF L597S, resulting only in tumor growth delay (PMID: 29903896). | 29903896 |
| BRAF L597S | melanoma | predicted - sensitive | Dabrafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment inhibited ERK activation and proliferation of melanoma cell lines harboring BRAF L597S in culture, but did not result in tumor shrinkage as a single agent in a melanoma patient-derived xenograft (PDX) model harboring BRAF L597S (PMID: 29903896). | 29903896 | |
| BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). | 29903896 |
| BRAF L597S | Advanced Solid Tumor | sensitive | Vemurafenib | Preclinical | Actionable | In a preclinical study, treatment of cells expressing BRAF L597S with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). | 22798288 | |
| BRAF R239Q BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and induced tumor shrinkage in 25% (3/12) of tumors and delayed tumor growth in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
| BRAF R239Q BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) increased growth inhibition in patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 67% of tumors, increased inhibition of ERK phosphorylation, and increased tumor growth delay compared to either agent alone in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
| BRAF R239Q BRAF L597S | melanoma | sensitive | Encorafenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and delayed tumor growth and induced shrinkage in 8% (1/12) of tumors in a melanoma patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 | |
| BRAF R239Q BRAF L597S | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a patient-derived melanoma cell line harboring BRAF L597S, as well as well as BRAF R239Q, in culture, and resulted in tumor shrinkage in 100% (13/13) of subcutaneous tumors, and decreased growth of intracranial tumors in a patient-derived xenograft (PDX) model (PMID: 29903896). | 29903896 |
| BRAF 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 | |
| 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 V600E BRAF V600M | melanoma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with rapidly growing malignant melanoma harboring BRAF V600E and V600M achieved a 60% reduction in tumor size 1 week following treatment with Tafinlar (dabrafenib), and the tumor completely disappeared 1 month after beginning treatment (PMID: 23031422). | 23031422 | |
| BRAF class 3 | melanoma | predicted - sensitive | KIN-2787 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KIN-2787 treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring a BRAF class 3 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). | detail... | |
| BRAF T599dup | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) resulted in disease progression in two patients with metastatic melanoma harboring BRAF T599dup (PMID: 35319964). | 35319964 | |
| BRAF T599dup | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination resulted in partial metabolic remission within six weeks in a patient with metastatic melanoma harboring BRAF T599dup (PMID: 29494756). | 29494756 |
| BRAF T599dup | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical study, a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in partial responses in 4 patients with metastatic melanoma harboring BRAF T599dup, with one patient also harboring CTNNB1 I35T (PMID: 35319964). | 35319964 |
| BRAF T599dup | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a clinical case study, a combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in regression of lymphadenopathy, lung nodules, and subcutaneous nodules in a patient with metastatic melanoma harboring BRAF T599dup, and at 9 months from treatment initiation, a partial response was still observed (PMID: 35319964). | 35319964 |
| BRAF G466A | 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 1 patient harboring BRAF G466A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF G466A | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF G466A achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... | |
| BRAF G466A | lung adenocarcinoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in 1 and stable disease in 2 patients with lung adenocarcinoma harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G466A | gastrointestinal system cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gastrointestinal system cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G466A | prostate cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring BRAF G466A (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF I463W BRAF V600E | melanoma | resistant | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cells harboring BRAF V600E and expressing BRAF I463W or expressing BRAF V600E and I463W in cis demonstrated resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). | 31925410 | |
| BRAF D287H NRAS Q61K | melanoma | predicted - sensitive | LXH 254 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a melanoma cell line harboring BRAF D287H and NRAS Q61K was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model of melanoma (PMID: 33355204). | 33355204 | |
| BRAF 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 | 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 | 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 | 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 | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600K (n=19) had increased tumor mutational burden and greater response rates (53% vs. 29%, p=0.059), progression-free survival (19 vs. 2.7 months, p=0.049), and overall survival (20.4 vs. 11.7 months, p=0.081) relative to patients with BRAF V600E (n=84) when treated with Keytruda (pembrolizumab) (n=17 and 62 for BRAF V600K and V600E, respectively) or Opdivo (nivolumab) (n=2 and 22 for BRAF V600K and V600E, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). | 22663011 detail... detail... |
| BRAF V600K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). | detail... 27480103 detail... |
| BRAF V600K | melanoma | 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 | 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 | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Pembrolizumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). | detail... |
| BRAF V600K | 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 | Binimetinib + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). | 30959471 detail... |
| BRAF V600K | melanoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with melanoma harboring BRAF V600K (n=19) had increased tumor mutational burden and greater response rates (53% vs. 29%, p=0.059), progression-free survival (19 vs. 2.7 months, p=0.049), and overall survival (20.4 vs. 11.7 months, p=0.081) relative to patients with BRAF V600E (n=84) when treated with Keytruda (pembrolizumab) (n=17 and 62 for BRAF V600K and V600E, respectively) or Opdivo (nivolumab) (n=2 and 22 for BRAF V600K and V600E, respectively) (PMID: 30630828). | 30630828 | |
| BRAF V600K | 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 | colon cancer | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of colon cancer cells harboring BRAF V600K in culture (PMID: 30559419). | 30559419 | |
| BRAF V600K | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Pembrolizumab + Trametinib | Phase II | Actionable | In a Phase II trial (IMPemBra), Keytruda (pembrolizumab) in combination with short-term or intermittent Tafinlar (dabrafenib) plus Mekinist (trametinib) resulted in improved median progression-free survival compared to Keytruda (pembrolizumab) monotherapy (27.0 vs 10.6 mo, p=0.13) in patients with treatment-naive advanced melanoma harboring BRAF V600E (n=26) or V600K (n=6) mutations (J Clin Oncol 38: 2020 (suppl; abstr 10021); NCT02625337). | detail... |
| BRAF V600K NRAS Q61K | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | 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 | 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 | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 | |
| BRAF V600K NRAS Q61K | melanoma | decreased response | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | 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 | 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 | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124Q | melanoma | sensitive | VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124Q | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). | 25370473 |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 |
| BRAF V600K MAP2K1 P124L | melanoma | sensitive | VX-11e | Preclinical | Actionable | In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124L in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). | 25370473 | |
| BRAF V600K MAP2K1 P124L | melanoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease progression within one month in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124L (PMID: 31980996). | 31980996 |
| BRAF V600K MAP2K1 P124S | melanoma | predicted - resistant | Dabrafenib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) treatment resulted in disease progression within 5 weeks in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124S (PMID: 24265153). | 24265153 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | CI-1040 | Preclinical | Actionable | In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I in culture (PMID: 20538618). | 20538618 |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - resistant | SB590885 | Preclinical | Actionable | In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | predicted - sensitive | RAF265 | Preclinical | Actionable | In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). | 20538618 | |
| BRAF T529I BRAF V600E | Advanced Solid Tumor | 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 G466V | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced ERK signaling and inhibited proliferation of non-small cell lung cancer cell lines harboring BRAF G466V in culture (PMID: 28783719). | 28783719 |
| BRAF G466V | colorectal cancer | sensitive | Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Erbitux (cetuximab) reduced ERK signaling and resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF G466V, and wild-type RAS and NF1 (PMID: 28783719). | 28783719 | |
| BRAF G466V | colorectal cancer | sensitive | Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Erbitux (cetuximab) treatment inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). | 30559419 | |
| BRAF G466V | colorectal cancer | sensitive | Cetuximab + PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). | 30559419 | |
| BRAF G466V | lung cancer | predicted - sensitive | CFT1946 | Preclinical - Cell culture | Actionable | In a preclinical study, CFT1946 treatment inhibited proliferation of a lung cancer cell line harboring heterozygous BRAF G466V in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 2158). | detail... | |
| 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 | colorectal cancer | sensitive | Cetuximab + Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) inhibited tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V, but did not improve efficacy compared to Erbitux (cetuximab) treatment alone (PMID: 30559419). | 30559419 | |
| BRAF G466V | lung 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 | 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 G466V (PMID: 31924734; NCT02465060). | 31924734 |
| 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 | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring BRAF G466V in culture (PMID: 27523909). | 27523909 | |
| BRAF G466V | colorectal cancer | predicted - sensitive | Irinotecan + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colorectal cancer harboring BRAF G466V, and with wild-type RAS and NF1, demonstrated tumor regression following treatment with Vectibix (panitumumab) plus Camptosar (irinotecan) (PMID: 28783719). | 28783719 | |
| BRAF G466V | colorectal cancer | resistant | PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). | 30559419 | |
| BRAF G466V | 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 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 | lung cancer | predicted - sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, lung cancer cells harboring BRAF G466V demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). | 30559419 | |
| BRAF G466V | 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 | predicted - resistant | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF G466V (PMID: 30559419). | 30559419 | |
| BRAF G466V | colorectal cancer | predicted - resistant | 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 | 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 | 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 | 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 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 V504_R506dup | Advanced Solid Tumor | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Mekinist (trametinib) in culture (PMID: 30575814). | 30575814 |
| BRAF V504_R506dup | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Zelboraf (vemurafenib) in culture (PMID: 30575814). | 30575814 | |
| BRAF V504_R506dup | Advanced Solid Tumor | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human embryonic kidney cells overexpressing Braf V504_R506dup were resistant to Nexavar (sorafenib) in culture (PMID: 30575814). | 30575814 | |
| BRAF 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 K601E | colorectal cancer | resistant | Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Erbitux (cetuximab) treatment did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 | |
| BRAF K601E | 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 | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 6 of the non-responding patients harbored BRAF K601E (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF K601E | Advanced Solid Tumor | conflicting | 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 | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a melanoma patient harboring BRAF K601E demonstrated a 48% reduction in lymphadenopathy when treated with Mekinist (trametinib) and after more than 36 months of treatment showed a complete response (PMID: 28344857). | 28344857 |
| BRAF K601E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial, a melanoma patient harboring BRAF K601E demonstrated a partial response and a progression free survival of 32 weeks when treated with Mekinist (trametinib) (PMID: 23248257; NCT01037127). | 23248257 |
| BRAF K601E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | U0126 | Preclinical - Cell culture | Actionable | In a preclinical study, U0126 treatment inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). | 18794803 |
| BRAF K601E | melanoma | predicted - sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) treatment induced limited apoptosis and inhibited growth of melanoma cells harboring BRAF K601E in culture (PMID: 18794803). | 18794803 | |
| BRAF K601E | melanoma | no benefit | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in transient disease stabilization followed by metastatic progression in a patient with metastatic melanoma harboring BRAF K601E (PMID: 31182949). | 31182949 | |
| BRAF K601E | 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 | colorectal cancer | resistant | Cetuximab + Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Erbitux (cetuximab) treatment in combination with Zelboraf (vemurafenib) did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 | |
| BRAF K601E | lung adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in a partial response lasting at least nine months with near-complete tumor regression in a patient with lung adenocarcinoma harboring BRAF K601E (PMID: 34590045). | 34590045 |
| BRAF K601E | colorectal cancer | resistant | Vemurafenib | Preclinical - Pdx | Actionable | In a preclinical study, Zelboraf (vemurafenib) treatment did not inhibit tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 | |
| BRAF K601E | colorectal cancer | predicted - sensitive | PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment resulted in partial inhibition of tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 | |
| BRAF K601E | pancreatic endocrine carcinoma | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with Mekinist (trametinib) (PMID: 31158244). | 31158244 |
| BRAF K601E | 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 | Advanced Solid Tumor | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the MEK inhibitor, Mekinist (trametinib) decreased activation of MEK and ERK in cells expressing BRAF K601E in culture (PMID: 22798288). | 22798288 |
| BRAF K601E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) treatment resulted in a partial response in a patient with metastatic melanoma harboring BRAF K601E, increased inhibition of Erk1/2 phosphorylation in a melanoma cell line expressing BRAF K601E in culture, and increased tumor growth inhibition in a patient-derived xenograft (PDX) model compared to Mekinist (trametinib) alone (PMID: 30248172). | 30248172 |
| BRAF K601E | colorectal cancer | sensitive | Cetuximab + PLX8394 | Preclinical - Pdx | Actionable | In a preclinical study, PLX8394 treatment in combination with Erbitux (cetuximab) inhibited Erk signaling and reduced tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). | 30559419 | |
| BRAF K601E | 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 MAP2K1 V211D | colon cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | sensitive | MEK inhibitor (Pan) | MAP855 | Preclinical - Pdx | Actionable | In a preclinical study, MAP955 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | predicted - resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). | 31227518 |
| BRAF K601E MAP2K1 V211D | colon cancer | resistant | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
| BRAF 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 D594N | gallbladder cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a Phase II trial (BEAVER), Mektovi (binimetinib) and Braftovi (encorafenib) combination therapy resulted in stable disease in a patient with gallbladder cancer harboring BRAF D594N (J Clin Oncol 39, no. 15_suppl, abstr e15038; NCT03839342). | detail... |
| BRAF D594N | lung non-small cell carcinoma | predicted - sensitive | RMC-4550 | Preclinical - Pdx | Actionable | In a preclinical study, RMC-4550 treatment resulted in decreased Erk phosphorylation and dose-dependent tumor growth inhibition in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF D594N (PMID: 30104724). | 30104724 | |
| BRAF D594N | Advanced Solid Tumor | predicted - resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Mek in transformed cells expressing BRAF D594N in culture (PMID: 28783719). | 28783719 | |
| BRAF D594N | female reproductive organ cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with gynecological cancer harboring BRAF D594N (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF loss NRAS Q61K | melanoma | decreased response | LXH 254 | Preclinical - Cell culture | Actionable | In a preclinical study, CRISPR-Cas9 mediated knockout of BRAF in a melanoma cell line harboring NRAS Q61K led to decreased sensitivity to LXH254 treatment compared to parental cells harboring BRAF D287H and NRAS Q61K in culture (PMID: 33355204). | 33355204 | |
| BRAF G534D NRAS Q61L | melanoma | resistant | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of BRAF G534D in a melanoma cell line harboring NRAS Q61L conferred resistance to treatment with Belvarafenib (HM95573) in culture (PMID: 33953400). | 33953400 | |
| BRAF act mut | melanoma | no benefit | Sorafenib | Phase II | Actionable | In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). | 22394203 16880785 | |
| BRAF act mut | Advanced Solid Tumor | sensitive | 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 | colorectal cancer | no benefit | Venetoclax + VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 | |
| BRAF act mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 | |
| BRAF act mut | melanoma | 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 | 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 | 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 fusion | prostate cancer | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with prostate cancer harboring a BRAF fusion (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF fusion | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Guideline | Actionable | Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring a BRAF fusion (NCCN.org). | detail... |
| BRAF fusion | pilocytic astrocytoma | not applicable | N/A | Guideline | Diagnostic | BRAF fusions aid in the diagnosis of pilocytic astrocytoma (NCCN.org). | detail... | |
| BRAF fusion | pilocytic astrocytoma | not applicable | N/A | Guideline | Prognostic | BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (NCCN.org). | detail... | |
| BRAF G469A BRAF L584P | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in decrease in metastatic lesions and a partial response with 94% reduction at three months and continued metabolic response at six months in a patient with metastatic melanoma harboring BRAF G469A and BRAF L584P (PMID: 31569065). | 31569065 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | LY3009120 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated inhibition of Erk phosphorylation and greater inhibition of tumor growth when treated with the combination of Mekinist (trametinib) and LY3009120 compared to either agent alone (PMID: 34011980). | 34011980 |
| BRAF N486_P490del | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF N486_P490del | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with Mekinist (trametinib) (PMID: 34011980). | 34011980 |
| BRAF N486_P490del | 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 | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF N486_P490del | ovarian cancer | predicted - sensitive | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | 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 | LY3009120 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, a patient-derived xenograft (PDX) model with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del demonstrated partial inhibition of Erk phosphorylation and moderate inhibition of tumor growth when treated with LY3009120 (PMID: 34011980). | 34011980 | |
| BRAF N486_P490del | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to PD-0325901, resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF N486_P490del | ovarian cancer | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | ovarian cancer | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of an ovarian cancer cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | 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 | melanoma | predicted - sensitive | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated partial sensitivity to GDC0879 in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). | 26996308 |
| BRAF N486_P490del | melanoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | melanoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) failed to reduce phosphorylation of Mek and Erk and did not inhibit viability of a melanoma cell line harboring BRAF N486_P490del in culture (PMID: 26996308). | 26996308 | |
| BRAF N486_P490del | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical | Actionable | In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). | 26732095 |
| BRAF N486_P490del | ovarian cancer | 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 N486_P490del | ovarian cancer | sensitive | 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 L485Y | lung non-small cell carcinoma | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring BRAF L485Y were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). | 19276360 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a partial response in 38.5% (10/26) of patients with metastatic or unresectable, radioactive iodine-refractory papillary thyroid carcinoma harboring BRAF V600E that were multikinase inhibitor-naive, with a disease control rate of 73%, and a median progression-free survival of 18.2 months (PMID: 27460442; NCT01286753). | 27460442 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in a complete or partial response in three papillary thyroid carcinoma patients harboring BRAF V600E, with one patient having a response that lasted for 8 months who remained progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844; NCT00215605). | 20818844 | |
| BRAF V600E | 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 | 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 | colon cancer | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PKI-587) inhibited Braf V600E in vitro and inhibited growth of human colon cancer cells harboring BRAF V600E in culture (PMID: 21325073, PMID: 24042735). | 24042735 21325073 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | breast cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (TAPUR), Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy resulted in a complete response lasting 108.9 weeks in a patient with advanced breast cancer harboring BRAF V600E (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 3008; NCT02693535). | detail... |
| BRAF V600E | 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 | 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 | sensitive | C6-ceramide nanoliposome + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Nexavar (sorafenib) treatment in combination with C6-ceramide nanoliposome inhibited Mek and Akt phosphorylation, led to enhanced apoptosis and inhibition of proliferation, and synergistically reduced viability of melanoma cells harboring BRAF V600E in culture, and enhanced inhibition of tumor growth in a cell line xenograft model (PMID: 18519791). | 18519791 | |
| BRAF V600E | rectum cancer | sensitive | Cetuximab + Encorafenib | Guideline | Actionable | Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | 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 | colorectal cancer | predicted - resistant | BI-3406 | Preclinical - Cell culture | Actionable | In a preclinical study, BI-3406 treatment failed to inhibit growth of colorectal cancer cells harboring BRAF V600E in culture (PMID: 32816843). | 32816843 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in a colorectal cancer cell line harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | salivary gland cancer | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), a patient with salivary ductal carcinoma harboring BRAF V600E demonstrated a partial response when treated with Zelboraf (vemurafenib) (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | melanoma | 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 | 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 | anaplastic oligodendroglioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). | detail... |
| BRAF V600E | biliary tract cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | biliary tract cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) in combination with Mekinist (trametinib) demonstrated a manageable safety profile and resulted in an overall response rate of 51% (22/43, all partial responses) in patients with biliary tract cancer harboring BRAF V600E, with a median duration of response of 9 months, a median progression-free survival of 9 months, and a median overall survival of 14 months (PMID: 32818466; NCT02034110). | 32818466 |
| BRAF V600E | 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 | 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 | 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 | thyroid gland cancer | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | thyroid gland cancer | 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 | 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 | Vemurafenib | Phase I | Actionable | In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in an overall response rate of 81% (26/32; 2 complete responses, 24 partial responses), and inhibition of tumor Erk and Ccnd1, and reduced cell proliferation in metastatic melanoma patients harboring BRAF V600E (PMID: 20818844; NCT00215605). | 20818844 | |
| BRAF V600E | melanoma | sensitive | Vemurafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848, PMID: 21639808; NCT01006980), and BRAF V600E is included on the companion diagnostic (FDA.gov). | 28961848 detail... detail... 21639808 | |
| BRAF V600E | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E | colorectal cancer | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 27523909). | 27523909 | |
| BRAF V600E | melanoma | sensitive | 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 | neuroendocrine tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a rapid and sustained clinical response in a patient with a rectal neuroendocrine tumor harboring a BRAF V600E mutation (PMID: 27048246). | 27048246 |
| BRAF V600E | colorectal 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 | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) led to a partial response after 1 month of treatment in a metastatic pancreatic ductal adenocarcinoma patient harboring BRAF V600E, followed by disease progression, which was detected 12 months later (PMID: 35382161). | 35382161 |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | 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 | 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 | colorectal cancer | sensitive | BI 882370 + Cetuximab | Preclinical | Actionable | In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Erbitux (cetuximab) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). | 26916115 | |
| BRAF V600E | colorectal cancer | predicted - sensitive | Dabrafenib + JSI-1187 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and JSI-1187 led to synergistic inhibition of tumor growth in a colorectal cancer cell line xenograft model harboring BRAF V600E (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). | detail... | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + RAF709 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with RAF709, Tafinlar (dabrafenib), and Mekinist (trametinib) in melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture (PMID: 33568355). | 33568355 |
| BRAF V600E | 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 | 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 | colorectal cancer | no benefit | Vemurafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). | 22281684 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | Phase II | Actionable | In a Phase II trial, Zelboraf (vemurafenib) did not demonstrate meaningful clinical activity as a single agent, resulted in partial response in 5% (1/21) and stable disease in 33% (7/21) of patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 26460303; NCT00405587). | 26460303 | |
| BRAF V600E | colorectal cancer | no benefit | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, colorectal cancer cell lines harboring BRAF V600E demonstrated decreased response to Zelboraf (vemurafenib) in culture (PMID: 27312529). | 27312529 | |
| BRAF V600E | high grade glioma | no benefit | ZM336372 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ZM336372 treatment did not lead to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | basal cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in stable disease after three months of treatment in a patient with basal cell carcinoma harboring BRAF V600E (PMID: 33537843) | 33537843 |
| BRAF V600E | lung non-small cell carcinoma | not predictive | Atezolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab) compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | colorectal cancer | decreased response | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, treatment with Keytruda (pembrolizumab), Opdivo (nivolumab), or combination treatment with Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with mismatch repair-deficient colorectal cancer harboring BRAF V600E vs. patients with wild-type BRAF resulted in a lower objective response rate (44.4% vs. 74.2%, p = 0.12) and shorter progression-free survival (PFS) rates (1-year PFS 40% vs. 73.3%, 2-year PFS 26.7% vs. 73.3%) (PMID: 33631043). | 33631043 | |
| BRAF V600E | thyroid gland Hurthle cell carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid Hurthle cell carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | high grade glioma | sensitive | LY3009120 + Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, combination treatment with Zelboraf (vemurafenib) and LY3009120 treatment led to greater inhibition of cell growth compared to either agent alone in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). | 34433654 | |
| BRAF V600E | melanoma | predicted - resistant | KRT-232 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E demonstrated resistance to treatment with KRT-232 (AMG 232) (PMID: 32234759). | 32234759 | |
| BRAF V600E | 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 | 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 | thyroid gland follicular carcinoma | sensitive | Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid follicular carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | high grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 33% (15/45, 3 complete responses, 12 partial responses) in patients with high-grade glioma harboring BRAF V600E, with a median duration of response of 36.9 months, a median progression-free survival of 3.8 months, and an overall survival of 17.6 months (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | 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 | 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 | 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 | anaplastic astrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in 1 of 5 patients with anaplastic astrrocytoma harboring BRAF V600E, with 2 other patients achieved stable disease lasting 14.9, and 5.6 months, respectively (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | melanoma | 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 | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | IMM-1-104 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, IMM-1-104 treatment led to tumor growth inhibition in a cell line xenograft model of melanoma harboring BRAF V600E (Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P252). | detail... |
| BRAF V600E | pilocytic astrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with pilocytic astrrocytoma harboring BRAF V600E who stayed on treatment for 15.3 months (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | melanoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + KRT-232 + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, the addition of KRT-232 (AMG 232) to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in a synergistic effect, leading to a greater decrease in tumor growth and tumor size compared to either KRT-232 (AMG 232) alone or Tafinlar (dabrafenib) plus Mekinist (trametinib) in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E (PMID: 32234759). | 32234759 |
| BRAF V600E | pilocytic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | 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 | skin melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with YM-254890 and Mekinist (trametinib) did not result in synergistic inhibition of cell viability of a cutaneous melanoma cell line harboring BRAF V600E in culture (PMID: 33229459). | 33229459 |
| BRAF V600E | melanoma | sensitive | 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 | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with epithelioid glioblastoma harboring BRAF V600E continued to response as Cotellic (cobimetinib) was added to Zelboraf (vemurafenib) treatment (PMID: 31217909). | 31217909 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | 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 | 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 | 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 | pancreatic acinar cell adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with pancreatic acinar cell carcinoma harboring BRAF V600E who had previously progressed on chemotherapy led to a response at 8 weeks, and ongoing clinical and radiological response was still observed at 32 months of treatment (PMID: 33537843). | 33537843 |
| BRAF V600E | lung non-small cell carcinoma | predicted - sensitive | LTT462 + LXH 254 | Case Reports/Case Series | Actionable | In a Phase Ib trial, LTT462 and LXH 254 combination therapy was well tolerated and resulted in an unconfirmed partial response (PR) in 4% (2/49) and stable disease (SD) in 33% (16/49) of patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer, with 1 patient harboring BRAF V600E achieving an unconfirmed PR and 1 achieving SD with over 25% tumor reduction (Ann Oncol 31 (suppl 4):S881-S882; NCT02974725). | detail... | |
| BRAF V600E | anaplastic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Guideline | Actionable | Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
| BRAF V600E | anaplastic pleomorphic xanthoastrocytoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in an ongoing partial response 8 months after initiation of treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, and a near complete response after 3 months of treatment in another patient with relapsed disease (PMID: 28984141). | 28984141 |
| BRAF V600E | colon adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Regorafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a patient with colon adenocarcinoma harboring BRAF V600E led to stable disease, and treatment continued for eight months, at which time some disease progression was observed (PMID: 33568355). | 33568355 |
| BRAF V600E | thyroid gland carcinoma | predicted - sensitive | Dabrafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Tafinlar (dabrafenib) treatment resulted in a partial response in 29% (4/14) and stable disease in 43% (6/14) of patients with thyroid carcinoma harboring BRAF V600E, with 64% (9/14) of patients achieved at least a 10% decrease by RECIST, and a median progression-free survival of 11.3 months among responders (PMID: 25285888; NCT00880321). | 25285888 | |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | Case Reports/Case Series | Actionable | In a clinical case study, Braftovi (encorafenib) and Mektovi (binimetinib) combination therapy resulted in durable stable disease lasting at least 3.5 years in a patient with low-grade serous ovarian carcinoma harboring BRAF V600E, who was previously treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33043759). | 33043759 |
| BRAF V600E | colorectal cancer | sensitive | 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 | 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 | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial (ROAR) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an overall response rate of 61% (20/33; 3 complete responses, 17 partial responses) in patients with anaplastic thyroid cancer harboring BRAF V600E, with 12-month duration of response rate of 50%, a median progression-free survival and overall survival of 6.7 and 14.5 months, respectively (PMID: 35026411; NCT02034110). | 35026411 detail... detail... detail... |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Clinical Study | Actionable | In a clinical case report, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in a clinical and radiologic response that lasted for 9 months in an anaplastic thyroid cancer patient harboring BRAF V600E (PMID: 27697975). | 27697975 |
| BRAF V600E | thyroid gland anaplastic carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with advanced or metastatic thyroid gland anaplastic carcinoma harboring BRAF V600E (PMID: 31549998, PMID: 35491008; ESMO.org). | 31549998 detail... 35491008 |
| BRAF V600E | 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 | cholangiocarcinoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), responses were seen in patients with cholangiocarcinoma harboring BRAF V600E (n=9) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). | 32029534 | |
| BRAF V600E | melanoma | sensitive | SBI-755199 | Preclinical | Actionable | In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). | 26603897 | |
| BRAF V600E | melanoma | sensitive | 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 | skin melanoma | no benefit | YM-254890 | Preclinical - Cell culture | Actionable | In a preclinical study, YM-254890 treatment did not inhibit cell viability of a cutaneous melanoma cell line harboring BRAF V300E in culture (PMID: 33229459). | 33229459 | |
| BRAF V600E | lung adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with lung adenocarcinoma, 1 achieved a partial response with an ongoing progression-free survival (PFS) at 32.5 mo, 3 patients had stable disease for 15.6, 6.6, and 3.6 mo, and an additional unevaluable patient achieved an 81% reduction of measured lesions and a PFS of 12.7 mo (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | 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 | Clinical Study | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E achieved an overall response rate of 54% (13/24, 2 complete responses, 11 partial responses, and 10 with stable disease) and a disease control rate of 96% following treatment with Zelboraf (vemurafenib) (PMID: 26200454). | 26200454 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | Phase II | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 43% (6/14, 1 complete response, 5 partial response) in patients with non-small cell lung cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 2 patients (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF V600E | lung non-small cell carcinoma | sensitive | Vemurafenib | 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 | anaplastic astrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). | detail... |
| BRAF V600E | 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 | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib) led to a partial response after 1 month of treatment in a microsatellite stable pancreatic ductal adenocarcinoma patient with BRAF V600E and amplification of FGFR1 and NOTCH2, with significant decrease in hepatic metastatic lesions and undetectable lung lesions at 6 months, and a progression-free survival of at least 6 months (PMID: 35382161). | 35382161 |
| BRAF V600E | 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 | 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 | colon cancer | resistant | Cetuximab | Guideline | Actionable | Erbitux (cetuximab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab + Encorafenib | Phase II | Actionable | In a Phase II (ANCHOR CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment (n=95) demonstrated an acceptable safety profile and resulted in a confirmed response rate of 47.8%, a disease control rate of 88%, a median progression-free survival of 5.8 months, and a median overall survival of 17.2 months in patients with metastatic colorectal cancer harboring BRAF V600E (Ann Oncol Volume 32, Supplement 3, July 2021, Page S222; NCT03693170). | detail... |
| BRAF V600E | colorectal cancer | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Cetuximab + Encorafenib | Phase III | Actionable | In a Phase III (BEACON CRC) trial, Braftovi (encorafenib), Mektovi (binimetinib), and Erbitux (cetuximab) combination treatment (n=111) resulted in improved median overall survival (9.0 vs 5.4 months, HR=0.52, p<0.001), confirmed response rate (26% vs 2%, p<0.001), and median progression-free survival (4.3 vs 1.5 months, HR=0.38, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). | 31566309 |
| BRAF V600E | 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 | pleomorphic xanthoastrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in clinical benefit that lasted for more than 14 months in a patient with pleomorphic xanthoastrocytoma harboring BRAF V600E (PMID: 29632053). | 29632053 |
| BRAF V600E | pleomorphic xanthoastrocytoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy is included in guidelines as an adjuvant treatment for patients with pleomorphic xanthoastrocytoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth, downstream MAPK signaling and soft agar growth in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26343583). | 26343583 | |
| BRAF V600E | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | 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 | 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 | 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 | melanoma | sensitive | KRT-232 + Navitoclax | Preclinical - Pdx | Actionable | In a preclinical study, the combination of KRT-232 (AMG 232) and Navitoclax (ABT-263) resulted in a greater response than either drug alone in patient-derived xenograft (PDX) models of melanoma harboring BRAF V600E, leading to tumor regression (PMID: 32234759). | 32234759 | |
| BRAF V600E | 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 | 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 | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Chloroquine + Trametinib | Preclinical - Pdx | Actionable | In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a colorectal cancer patient-derived xenograft (PDX) model harboring BRAF V600E (PMID: 30833748). | 30833748 |
| BRAF V600E | pancreatic ductal adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Gemcitabine + Nab-paclitaxel | Case Reports/Case Series | Actionable | In a clinical case study, Gemzar (gemcitabine), Abraxane (nab-paclitaxel), and Cotellic (cobimetinib) combination treatment resulted in a complete radiologic response within 6 months of initiation lasting at least 16 months in a patient with microsatellite stable, KRAS wild-type pancreatic ductal adenocarcinoma harboring BRAF V600E (PMID: 34667063). | 34667063 |
| BRAF V600E | Advanced Solid Tumor | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Phase II | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with BRAF V600E positive advanced solid tumors other than melanoma, thyroid cancer, or colorectal cancer, with a median duration of response of 25.1 months, and a disease control rate of 75.9% (22/29) (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in tumor regression as confirmed by MRI after 3-weeks of treatment in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 31217909). | 31217909 | |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in stable disease as best response in 3 of 6 patients with glioblastoma harboring BRAF V600E, with stable disease lasting 3.6, 3.7, and 12.9 months, respectively (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | glioblastoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response 1 week after treatment in a patient with epithelioid type glioblastoma harboring BRAF V600E, although the patient soon passed due to complications (PMID: 31386052). | 31386052 | |
| BRAF V600E | 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 | 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 | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in significant clinical improvement in a patient with epithelioid glioblastoma harboring BRAF V600E, however, her disease progressed after 3 months of therapy (PMID: 31217909). | 31217909 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in a complete resolution of symptoms and radiographic partial response after the first treatment in a patient with glioblastoma harboring BRAF V600E whose disease progressed on PLX8394 treatment, and a complete response after 11 months of treatment, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904). | 32923904 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, an epithelioid glioblastoma patient harboring BRAF V600E treated with Mekinist (trametinib) and Tafinlar (dabrafenib) combination therapy resulted in stable disease, and the patient continued to demonstrate stable disease at least 16 months after initiation of therapy (PMID: 29632053). | 29632053 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination therapy of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in improved clinical symptoms in a patient with epithelioid glioblastoma harboring BRAF V600E, and treatment of the patient's cells resulted in decreased cell viability, reduced phosphorylation of Mek and Erk, increased apoptotic activity compared to either agent alone, and cell cycle arrest in culture, and led to tumor growth suppression in the patient-derived xenograft (PDX) model (PMID: 31345255). | 31345255 |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent glioblastoma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | glioblastoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response in 32% (10/31, 2 complete responses, 8 partial responses) and stable disease in 19% (6/31) of patients with glioblastoma harboring BRAF V600E (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | 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 | 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 | 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 | 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 | large cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical study, a patient with poorly differentiated large cell carcinoma harboring BRAF V600E experienced a complete response lasting at least 2 years on combination treatment with Cotellic (cobimetinib) and Zelboraf (vemurafenib) (PMID: 35046062). | 35046062 |
| BRAF V600E | melanoma | sensitive | 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 | 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 | high grade glioma | predicted - sensitive | Everolimus + PLX4720 | Preclinical - Cell culture | Actionable | In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). | 27217440 | |
| BRAF V600E | colon cancer | sensitive | Encorafenib + Panitumumab | Guideline | Actionable | Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | ASTX029 + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with ASTX029 and Zelboraf (vemurafenib) resulted in decreased viability of melanoma cells harboring BRAF V600E compared to either agent alone in culture (PMID: 34330842). | 34330842 | |
| BRAF V600E | 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 | thyroid gland cancer | sensitive | Dabrafenib + SCH772984 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with Tafinlar (dabrafenib) and SCH772984 synergistically inhibited cell growth of thyroid cancer cell lines harboring BRAF V600E in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 33595872). | 33595872 | |
| BRAF V600E | colorectal cancer | sensitive | 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 | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). | 23629727 |
| BRAF V600E | melanoma | sensitive | PLX4720 + Vorinostat | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of PLX4720 and Zolinza (vorinostat) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Rb phosphorylation in culture (PMID: 27924459). | 27924459 | |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). | detail... 30219628 detail... detail... |
| BRAF V600E | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Binimetinib + Encorafenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453), and both BRAF V600E and V600K are on the companion diagnostic. | 29573941 detail... detail... detail... |
| BRAF V600E | melanoma | sensitive | DETD-35 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). | 27048951 | |
| BRAF V600E | melanoma | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Cobimetinib + Pembrolizumab + Vemurafenib | Phase I | Actionable | In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). | detail... |
| BRAF V600E | 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 | melanoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | BGB-283 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) led to greater inhibition of growth in melanoma cell lines harboring BRAF V600E in culture compared to either treatment alone (PMID: 33318037). | 33318037 |
| BRAF V600E | 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 | 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 | 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 | intrahepatic cholangiocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with intrahepatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to stable disease at 6 weeks, improvement of lung and liver lesions at 12 weeks after treatment, and response was maintained until disease progression in the liver was observed at 10 months (PMID: 33537843). | 33537843 |
| BRAF V600E | 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 | 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 | lung papillary adenocarcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in regression of the lesions in the chest, abdomen and brain in a patient with lung papillary carcinoma harboring BRAF V600E but progression was observed 3 months later (PMID: 34178685). | 34178685 |
| BRAF V600E | ganglioglioma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with anaplastic ganglioglioma harboring BRAF V600E who stayed on treatment for 13.8 months (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | 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 | high grade glioma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Everolimus + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) and Afinitor (everolimus) synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). | 27217440 |
| BRAF V600E | 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 | Erdheim-Chester disease | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN.org). | detail... | |
| BRAF V600E | 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 | 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 | glioblastoma | decreased response | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PLX4720, demonstrating increased viability of CD133 positive cells in culture and in xenograft models (PMID: 26573800). | 26573800 | |
| BRAF V600E | melanoma | 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 | 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 | no benefit | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Selumetinib | Clinical Study - Cohort | Actionable | In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including BRAF V600E, activating KRAS, HRAS, or NRAS mutations, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620). | detail... |
| BRAF V600E | colon cancer | sensitive | PLX4720 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). | 18287029 | |
| BRAF V600E | melanoma | sensitive | 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 | 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 | 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 | 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 | ERAS-007 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation and Erk signaling in a melanoma cell line harboring BRAF V600E in culture, and inhibited tumor growth in patient-derived xenograft (PDX) models, including a Zelboraf (vemurafenib)-resistant PDX model (PMID: 34337566). | 34337566 | |
| BRAF V600E | 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 | 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 | 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 | 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 | lung non-small cell carcinoma | not predictive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). | 29723688 | |
| BRAF V600E | 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 | 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 | ovarian cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines as recurrence therapy for patients with ovarian cancer harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | diffuse large B-cell lymphoma | sensitive | ERAS-007 | Preclinical - Cell culture | Actionable | In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of diffuse large B-cell lymphoma cells harboring BRAF V600E in culture (PMID: 34337566). | 34337566 | |
| BRAF V600E | melanoma | sensitive | 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 | glioblastoma | sensitive | BI2536 | Preclinical - Cell culture | Actionable | In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated sensitivity to BI2536 in culture (PMID: 26573800). | 26573800 | |
| BRAF V600E | 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 | colorectal adenocarcinoma | sensitive | ASTX029 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation and inhibited growth of colorectal adenocarcinoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 34330842). | 34330842 | |
| BRAF V600E | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + LXH 254 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment with LXH 254, Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). | 33568355 |
| BRAF V600E | 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 | melanoma | sensitive | LY3214996 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LY3214996 treatment in a melanoma cell line harboring BRAF V600E led to decreased cell proliferation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 31744895). | 31744895 | |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase II | Actionable | In a Phase II trial (ROAR), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in an objective response rate of 69% (9/13, 1 complete response, 6 partial responses, 2 minor responses) in patients with low-grade glioma harboring BRAF V600E, with median duration of response, median progression-free survival, and overall survival time unreached (PMID: 34838156; NCT02034110). | 34838156 |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Phase Ib/II | Actionable | In a Phase I/II trial (Study X2101), Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment demonstrated manageable toxicity and resulted in an objective response rate of 25% (9/36, 1 complete response, 8 partial responses) and stable disease in 67% (24/36) of pediatric patients with pretreated low-grade glioma harboring BRAF V600E (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02124772). | detail... |
| BRAF V600E | low grade glioma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Guideline | Actionable | Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). | detail... |
| BRAF V600E | ovarian serous carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 5 patients with low grade serous ovarian carcinoma, 4 achieved a partial response (PR), 1 had stable disease, 3 of the PRs lasted over 12 months (PMID: 32758030; NCT02465060). | 32758030 |
| BRAF V600E | 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 | 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 | BGB659 | Preclinical - Cell culture | Actionable | In a preclinical study, BGB659 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). | 30559419 | |
| BRAF V600E | melanoma | 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 | 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 | 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 | pleomorphic xanthoastrocytoma | predicted - sensitive | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 42.9% (3/7, 1 complete response, 2 partial responses) and a clinical benefit rate of 57% in patients with pleomorphic xanthoastrocytoma harboring BRAF V600E, with a median progression-free survival of 5.7 months, and median overall survival not reached (PMID: 30351999; NCT01524978). | 30351999 | |
| BRAF V600E | 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 | 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 | 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 | 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 | 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 | 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 | 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 | thyroid gland papillary carcinoma | sensitive | Dabrafenib | Clinical Study - Cohort | Actionable | In a clinical study, Tafinlar (dabrafenib) treatment stimulated radioiodine uptake in 60% (6/10) of patients with metastatic iodine-refractory papillary thyroid cancer harboring BRAF V600E (PMID: 25549723; NCT01534897). | 25549723 | |
| BRAF V600E | thyroid gland papillary carcinoma | sensitive | Dabrafenib | Guideline | Actionable | Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). | detail... | |
| BRAF V600E | melanoma | sensitive | RXDX-105 | Preclinical - Cell line xenograft | Actionable | In preclinical studies, CEP-32496 (RXDX-105) reduced tumor volume and promoted tumor regression in xenograft models of a BRAF V600E mutant human melanoma cell line (PMID: 22319199). | 22319199 | |
| BRAF V600E | melanoma | 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). |