Molecular Profile Detail

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Profile Name BRAF P731T
Gene Variant Detail

BRAF P731T (unknown)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF T529I BRAF V600E Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529I to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF T529I BRAF V600E Advanced Solid Tumor sensitive 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 - 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 - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF T529I BRAF V600E Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529I were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF T529M BRAF V600E Advanced Solid Tumor predicted - sensitive RAF265 Preclinical Actionable In a preclinical study, RAF265 inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF T529M BRAF V600E Advanced Solid Tumor predicted - sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited kinase activity in vitro, and downstream Erk phosphorylation in cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M to a similar degree as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF T529M BRAF V600E Advanced Solid Tumor predicted - resistant PLX4720 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to PLX4720-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF T529M BRAF V600E Advanced Solid Tumor predicted - resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529M were insensitive to SB590885-mediated inhibition of ERK signaling in culture (PMID: 20538618). 20538618
BRAF T529M BRAF V600E Advanced Solid Tumor predicted - sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation in transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529M in culture (PMID: 20538618). 20538618
BRAF L485_P490delinsY lung non-small cell carcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, a non-small cell lung carcinoma cell line harboring BRAF L485_P490delinsY was sensitive to Mekinist (trametinib), resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF L485_P490delinsY lung non-small cell carcinoma resistant 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 L597K melanoma predicted - sensitive 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 mutant melanoma predicted - sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring a BRAF mutation (PMID: 29247021). 29247021
BRAF mutant lung non-small cell carcinoma 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 lung non-small cell carcinoma predicted - sensitive unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, mutant BRAF correlated with prolonged duration on immune checkpoint inhibitor therapy compared to wild-type BRAF in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). detail...
BRAF mutant cervix carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma 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 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 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 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 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 predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant lung non-small cell carcinoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant non-small cell lung cancer harboring (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant Advanced Solid Tumor 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 lymphoma no benefit Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion (n=1) or non-V600 mutations (n=31), resulted in a partial response in 3% (1/32) and stable disease in 31% (10/32) of the patients, with a median progression-free survival of 1.8 months, and a median overall survival of 5.7 months (PMID: 31924734; NCT02465060). 31924734
BRAF mutant melanoma sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) treatment resulted in an overall response rate (ORR) of 60% (15/25) and a median progression-free survival (mPFS) of 12.4 months in BRAF inhibitor-naïve melanoma patients harboring BRAF mutations, and an ORR of 22% (6/29) and mPFS of 1.9 months in BRAF inhibitor-pretreated patients (PMID: 28611198; NCT01436656). 28611198
BRAF mutant melanoma predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant melanoma sensitive 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 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 colon cancer predicted - sensitive 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 colorectal cancer sensitive 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 melanoma sensitive PET-16 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, PET-16 and Zelboraf (vemurafenib) synergistically inhibited growth of melanoma cell lines in culture, resulted in enhanced tumor growth inhibition in cell ine xenograft models (PMID: 26984758). 26984758
BRAF mutant Advanced Solid Tumor sensitive Obatoclax Preclinical Actionable In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with BRAF mutation in culture (PMID: 22460902). 22460902
BRAF mutant 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 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 thyroid gland cancer sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant thyroid cancer cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant melanoma sensitive 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 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 lung non-small cell carcinoma predicted - sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis and enhanced ERK inhibition compared to either agent alone in non-small cell lung cancer cell lines harboring non-BRAF V600 mutations in culture (PMID: 28947956). 28947956
BRAF mutant Advanced Solid Tumor no benefit 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 colorectal cancer no benefit Regorafenib Phase II Actionable In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). 30120161
BRAF mutant colorectal cancer predicted - sensitive Dabrafenib + Panitumumab + Trametinib Phase Ib/II Actionable In a Phase I/II trial, treatment with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and Vectibix (panitumumab) resulted in an objective response rate (ORR) of 21% and median progression-free survival (mPFS) of 4.2 mo, compared with 0% ORR and mPFS of 2.6 mo with Mekinist (trametinib) plus Vectibix (panitumumab), and 10% ORR and mPFS of 3.5 mo with Tafinlar (dabrafenib) plus Vectibix (panitumumab) in patients with BRAF-mutant colorectal cancer (PMID: 27770002; NCT01750918). 27770002
BRAF mutant melanoma sensitive MLN2480 Phase I Actionable In a Phase I trial, MLN2480 resulted in a median progression free survival of 4.6 months and a partial response in 50% (8/16) of melanoma patients harboring a BRAF mutation (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 410P; NCT01425008). detail...
BRAF mutant melanoma sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant melanoma predicted - sensitive 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 multiple myeloma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant Advanced Solid Tumor predicted - sensitive 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 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 colorectal cancer sensitive MLN2480 Preclinical Actionable In a preclinical study, MLN2480 demonstrated efficacy in BRAF mutant xenograft models of melanoma and colorectal cancer (J Clin Oncol 31, 2013 (suppl; abstr e13529)). detail...
BRAF mutant melanoma sensitive 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 pancreatic adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human pancreatic adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant melanoma sensitive 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 Advanced Solid Tumor predicted - sensitive 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 Advanced Solid Tumor predicted - sensitive LXH 254 Case Reports/Case Series Actionable In a Phase I trial, LXH 254 treatment resulted in partial response in 2.6% (2/75) and stable disease in 33% (25/75) of patients with advanced solid tumors harboring MAPK pathway alterations, one of the patient achieved partial response harbored a BRAF mutation (J Clin Oncol 36, no. 15_suppl (May 20 2018) 2586-2586; NCT02607813). detail...
BRAF mutant colorectal cancer predicted - sensitive SY-5609 Preclinical - Pdx Actionable In a preclinical study, SY-5609 treatment resulted in 90% or more tumor growth inhibition or tumor regression in 50% (5/10) of patient-derived xenograft (PDX) models of colorectal cancer harboring BRAF mutations (J Clin Oncol 38: 2020 (suppl; abstr 3585)). detail...
BRAF mutant Advanced Solid Tumor 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 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 thyroid gland cancer predicted - sensitive Selumetinib Phase I Actionable In a Phase I study, Koselugo (selumetinib) demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine, including patients with BRAF and NRAS mutations (PMID: 23406027). 23406027
BRAF mutant melanoma 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 PF-00477736 + PF3644022 Preclinical - Cell line xenograft Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of various cancer cell lines harboring BRAF mutations in culture and in cell line xenograft models (PMID: 26140595). 26140595
BRAF mutant melanoma sensitive 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 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 melanoma sensitive E6201 + LY294002 Preclinical Actionable In a preclinical study, E6201 and LY294002 synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations in culture, regardless of PTEN mutation status (PMID: 23039341). 23039341
BRAF mutant colorectal cancer sensitive Belvarafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Belvarafenib (HM95573) inhibited growth of BRAF mutant colorectal cancer cell lines in culture and in cell line xenograft models (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). detail...
BRAF mutant Advanced Solid Tumor 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 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 lung adenocarcinoma sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of lung adenocarcinoma cells harboring mutant BRAF in culture (PMID: 26343583). 26343583
BRAF mutant melanoma predicted - sensitive 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 colorectal cancer sensitive Alpelisib + Cetuximab + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, the triple combination therapy of Encorafenib (LGX818), Erbitux (cetuximab), and Alpelisib (BYL719) resulted in an overall response rate of 18% (5/28), including 5 patients with a partial response, and led to a median progression free survival of 4.2 months and response duration of 12 weeks (PMID: 28363909). detail... 28363909
BRAF mutant melanoma 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 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 colorectal cancer resistant 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 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 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 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 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 pancreatic cancer predicted - sensitive KO-947 Preclinical - Pdx Actionable In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of BRAF-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). detail...
BRAF mutant colorectal cancer predicted - sensitive 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 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 Pimasertib + SAR405838 Phase I Actionable In a Phase I trial, SAR405838 and Pimasertib (MSC1936369B) combination therapy demonstrated safety and preliminary efficacy, resulted in partial response in 4% (1/24) and stable disease in 63% (15/24) of patients with TP53 wild-type advanced solid tumors harboring RAS/RAF mutations (KRAS, n=24; BRAF, n=1; NRAS, n=1) (PMID: 30585255; NCT01985191). 30585255
BRAF mut TP53 wild-type melanoma sensitive KRT-232 Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). 25567130
BRAF mut TP53 wild-type melanoma sensitive 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 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 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 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 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 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 mut melanoma decreased response 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 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 sensitive 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 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 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 AZD6482 + NVP-AEW541 Preclinical Actionable In a preclinical study, AZD6482 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit AZD6482 + Binimetinib Preclinical Actionable In a preclinical study, AZD6482 and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN wild-type melanoma no benefit 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 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 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 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 TGX-221 Preclinical Actionable In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma no benefit Alpelisib + NVP-AEW541 Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut 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 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 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 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 AZD6482 + Encorafenib + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + 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 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 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 no benefit Alpelisib + Binimetinib Preclinical Actionable In a preclinical study, Alpelisib (BYL719) and Binimetinib (MEK162) combination treatment did not enhance growth inhibition compared to single agent in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive 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 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 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 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 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 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 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 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 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 Encorafenib + GSK2636771 + unspecified IGF-1R antibody Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment consisting of GSK2636771, Encorafenib (LGX818), and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Encorafenib Preclinical Actionable In a preclinical study, AZD6482 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive Encorafenib + GSK2636771 Preclinical Actionable In a preclinical study, GSK2636771 and Encorafenib (LGX818) synergistically inhibited proliferation of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive AZD6482 + Binimetinib + Encorafenib + NVP-AEW541 Preclinical Actionable In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). 26577700
BRAF mut PTEN inact mut melanoma sensitive 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 RB1 loss melanoma decreased response Palbociclib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). 27488531
BRAF mut RB1 loss melanoma decreased response 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 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 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 V600K melanoma sensitive Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). detail... 27480103 detail...
BRAF V600K melanoma no benefit Cobimetinib + Pembrolizumab + Vemurafenib Phase I Actionable In a Phase I trial, combination of Cotellic (cobimetinib), Zelboraf (vemurafenib), and Keytruda (pembrolizumab) resulted in unreached median progression-free survival and overall survival in patients with advanced melanoma harboring BRAF V600E or V600K mutations, however, the trial was closed due to high incidence of dose-limiting toxicity and decreased health utility at 1 year (J Clin Oncol 39, no. 15_suppl, abstract e21506; NCT02818023). detail...
BRAF V600K lung non-small cell carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a objective response rate of 44.8% (43/96), median duration of response of 6.4 months, median progression-free survival (PFS) of 5.2 months, and median overall survival of 10 months in non-small cell lung cancer patients with BRAF V600 mutations, with a PFS of 2.1 and 6.8 months in the 2 patients harboring BRAF V600K (PMID: 31959346; NCT02304809). 31959346
BRAF V600K 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 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 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 skin melanoma sensitive Cobimetinib + Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600K melanoma 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 skin melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600K, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600K melanoma sensitive Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K-positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011 detail... detail...
BRAF V600K melanoma sensitive GSK2126458 Preclinical Actionable In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). 22389471
BRAF V600K skin melanoma sensitive Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600K, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600K melanoma sensitive 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 Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). detail... 30219628 detail... detail...
BRAF V600K melanoma predicted - sensitive 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 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 decreased response 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 + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). 22389471
BRAF V600K NRAS Q61K melanoma sensitive 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 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 MAP2K1 P124Q melanoma sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124Q melanoma sensitive VX-11e Preclinical - Cell culture Actionable In a preclinical study, VX-11e inhibited ERK signaling and reduced growth of a melanoma cell line harboring BRAF V600K and MAP2K1 P124Q in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600K and MAP2K1 P124L demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 25370473). 25370473
BRAF V600K MAP2K1 P124L melanoma sensitive 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 predicted - resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease progression within one month in a metastatic melanoma patient harboring BRAF V600K and MAP2K1 P124L (PMID: 31980996). 31980996
BRAF V600K MAP2K1 P124L melanoma sensitive 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 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 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 G464V lung adenocarcinoma no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with lung adenocarcinoma harboring BRAF G464V (PMID: 31924734; NCT02465060). 31924734
BRAF G464V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464V (PMID: 26343582). 26343582
BRAF G464V Advanced Solid Tumor resistant Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G464V (PMID: 29320312; NCT02091141). 29320312
BRAF 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 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 G606E Advanced Solid Tumor no benefit Vemurafenib Clinical Study - Cohort Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 1 of the non-responding patients harbored BRAF G606E (PMID: 29320312; NCT02091141). 29320312
BRAF 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 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 hematologic cancer sensitive LY3009120 Preclinical - Cell culture Actionable In a preclinical study, a hematological tumor cell line harboring BRAF K601N demonstrated sensitivity to LY3009120 in culture (PMID: 26732095). 26732095
BRAF K601N lung non-small cell carcinoma 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 V600D melanoma sensitive Belvarafenib + Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Cotellic (cobimetinib) to treatment with Belvarafenib (HM95573) in a melanoma cell line harboring BRAF V600D resulted in greater inhibition of cell proliferation in culture compared to single agent alone (PMID: 33953400). 33953400
BRAF V600D melanoma sensitive ASTX029 Preclinical - Cell culture Actionable In a preclinical study, ASTX029 treatment inhibited growth of a melanoma cell line harboring BRAF V600D in culture (PMID: 34330842). 34330842
BRAF V600D pilocytic astrocytoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, single Tafinlar (dabrafenib) and subsequent Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in disease stablization in a patient with pilocytic astrocytoma harboring BRAF V600D (PMID: 28784858). 28784858
BRAF V600D melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive CCT241161 Preclinical Actionable In a preclinical study, CCT241161 inhibited MEK and ERK phosphorylation and growth of melanoma cells harboring BRAF V600D in culture (PMID: 25500121, PMID: 17210691). 25500121 17210691
BRAF V600D melanoma sensitive Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) inhibited proliferation of melanoma cells harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D 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 3.8 months in the patient harboring BRAF V600D (PMID: 31959346; NCT02304809). 31959346
BRAF V600D melanoma sensitive Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) inhibited proliferation of melanoma cells harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited proliferation of melanoma cell lines harboring BRAF V600D in culture (PMID: 27523909). 27523909
BRAF V600D melanoma sensitive CCT196969 Preclinical Actionable In a preclinical study, CCT196969 inhibited MEK and ERK phosphorylation and growth of melanoma cells harboring BRAF V600D in culture (PMID: 25500121, PMID: 17210691). 25500121 17210691
BRAF V600D PTEN loss melanoma sensitive XL147 Preclinical - Cell line xenograft Actionable In a preclinical study, XL147 inhibited tumor growth in xenograft models of a PTEN-deficient human melanoma cell line harboring BRAF V600D (PMID: 25637314). 25637314
BRAF V600D NRAS dec exp melanoma no benefit Binimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600D and knockdown of NRAS demonstrated a decreased response to Mektovi (binimetinib) relative to cells without NRAS knockdown in culture (PMID: 29245078). 29245078
BRAF L514V breast cancer resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) did not inhibit Erk and Mek signaling in breast cancer cells expressing BRAF L514V in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Trametinib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Mekinist (trametinib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response PLX8394 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to PLX8394-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3245 Preclinical - Cell culture Actionable In a preclinical study, BGB3245 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive SCH772984 Preclinical - Cell culture Actionable In a preclinical study, SCH772984 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Zelboraf (vemurafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response TAK-632 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to TAK-632-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma predicted - sensitive BGB3290 Preclinical - Cell culture Actionable In a preclinical study, BGB3290 resulted in similar inhibition of Erk phosphorylation and colony formation in melanoma cells expressing BRAF L514V in cis with V600E and cells expressing BRAF V600E alone in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E melanoma decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells expressing BRAF L514V in cis with V600E demonstrated decreased response to Tafinlar (dabrafenib)-induced inhibition of Erk phosphorylation and colony formation compared to cells expressing BRAF V600E in culture (PMID: 29880583). 29880583
BRAF L514V BRAF V600E ganglioglioma resistant Dabrafenib Case Reports/Case Series Actionable In a clinical case study, a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E progressed after initial response to Tafinlar (dabrafenib) treatment, and was found to have acquired a BRAF L514V in cis with BRAF V600E, which conferred dabrafenib resistance in culture (PMID: 29880583). 29880583
BRAF N486_T491delinsK lymphatic system cancer predicted - sensitive Cobimetinib Case Reports/Case Series Actionable In a Phase II trial, treatment with Cotellic (cobimetinib) in patients with histiocytic neoplasms resulted in a PET overall response rate of 89% (16/18), with complete response in 72% (13/18) and partial response in 17% (3/18), and resulted in stable disease in 6% (1/18) of patients, including a complete response in a patient with Langerhans cell histiocytosis harboring BRAF N486_T491delinsK (PMID: 30867592; NCT01953926). 30867592
BRAF N486_T491delinsK Advanced Solid Tumor predicted - sensitive Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, Cotellic (cobimetinib) inhibited viability of transformed cells expressing BRAF N486_T491delinsK in culture (PMID: 30867592). 30867592
BRAF fusion prostate cancer no benefit 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 not applicable N/A Guideline Prognostic BRAF fusions are associated with indolent disease in patients with pilocytic astrocytoma (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 sensitive 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 L597S melanoma sensitive 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 LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of melanoma cells harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive 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 Advanced Solid Tumor sensitive 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 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 Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in melanoma cell lines harboring BRAF L597S in culture (PMID: 29903896). 29903896
BRAF L597S melanoma sensitive 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 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 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 predicted - sensitive 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 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 L597S melanoma sensitive 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 R239Q BRAF L597S melanoma sensitive 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 Binimetinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Mektovi (binimetinib) inhibited growth of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and induced tumor shrinkage in 25% (3/12) of tumors and delayed tumor growth in a patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF R239Q BRAF L597S melanoma sensitive Encorafenib Preclinical - Pdx & cell culture Actionable In a preclinical study, Braftovi (encorafenib) inhibited ERK activation and proliferation of patient-derived melanoma cells harboring BRAF L597S, as well as BRAF R239Q, in culture, and delayed tumor growth and induced shrinkage in 8% (1/12) of tumors in a melanoma patient-derived xenograft (PDX) model (PMID: 29903896). 29903896
BRAF R239Q BRAF L597S melanoma sensitive 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 G469E breast ductal carcinoma predicted - sensitive 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 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 G469E melanoma resistant 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 sarcomatoid carcinoma no benefit 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 G596R colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not reduce activation of Erk and Mek in a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). 28783719
BRAF G596R lung non-small cell carcinoma no benefit Vemurafenib Case Reports/Case Series Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 1 patient harboring BRAF G596R, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G596R colorectal cancer sensitive Dabrafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28947956). 28947956
BRAF G596R colorectal cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) reduced Erk signaling and inhibited proliferation of a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). 28783719
BRAF G596R 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 G596R (PMID: 29320312; NCT02091141). 29320312
BRAF G596R colorectal cancer predicted - sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited Erk phosphorylation and proliferation of colorectal cancer cells harboring BRAF G596R in culture (PMID: 30104724). 30104724
BRAF G596R colorectal cancer predicted - sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF G596R demonstrated sensitivity to PLX8394 treatment in culture (PMID: 30559419). 30559419
BRAF G596R PIK3CA E545K colorectal cancer resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, colorectal cancer cells harboring BRAF G596R and PIK3CA E545K did not demonstrate sensitivity to Zelboraf (vemurafenib) treatment in culture (PMID: 22180495). 22180495
BRAF G596R PIK3CA E545K colorectal cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of colorectal cancer cells harboring both BRAF G596R and PIK3CA E545K in culture (PMID: 26243863). 26243863
BRAF 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 T599K 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 T599K in culture (PMID: 31158244). 31158244
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 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 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 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 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 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 S363F BRAF K601E melanoma sensitive 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 G469L lung adenocarcinoma no benefit Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring BRAF G469L did not respond to Zelboraf (vemurafenib) therapy (PMID: 24035431). 24035431
BRAF 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 conflicting Sorafenib Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to Nexavar (sorafenib)-mediated inhibition of Erk phosphorylation but were equally as sensitive to Nexavar (sorafenib)-mediated growth inhibition as transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF T529N BRAF V600E Advanced Solid Tumor resistant SB590885 Preclinical Actionable In a preclinical study, transformed cells expressing BRAF V600E and the gatepkeeper mutation BRAF T529N were insensitive to SB590885 in culture (PMID: 20538618). 20538618
BRAF T529N BRAF V600E Advanced Solid Tumor sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E and the gatekeeper mutation BRAF T529N in culture (PMID: 20538618). 20538618
BRAF T529N BRAF V600E Advanced Solid Tumor resistant 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 F595L Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, treatment with Zelboraf (vemurafenib) did not reduce activation of Mek and Erk by BRAF F595L in transformed cells in culture (PMID: 26582644). 26582644
BRAF G469V osteosarcoma no benefit Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in progressive disease in a patient with osteosarcoma of the renal pelvis harboring BRAF G469V (PMID: 31924734; NCT02465060). 31924734
BRAF G469V 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 G469V, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). 31959346
BRAF G469V lung non-small cell carcinoma predicted - sensitive Sorafenib Case Reports/Case Series Actionable In a clinical case study, a patient with synchronous BRAF wild-type hepatocellular carcinoma (HCC) and non-small cell lung cancer harboring BRAF G469V demonstrated a partial response in primary lung lesions, complete response in the lung metastasis, and stability of the HCC following treatment with Nexavar (sorafenib) (PMID: 27388325). 27388325
BRAF G469V Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469V (PMID: 26343582). 26343582
BRAF G469V lung adenocarcinoma no benefit Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a previously treated lung adenocarcinoma patient harboring BRAF G469V demonstrated progression after 9 weeks of treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (PMID: 32540409). 32540409
BRAF G469V melanoma no benefit Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) did not inhibit ERK phosphorylation or proliferation of a melanoma cell line harboring BRAF G469V (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive Encorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive Binimetinib + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma sensitive LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma predicted - resistant Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469V NRAS Q61K melanoma no benefit Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). 29903896
BRAF G469A BRAF W604C lung adenocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination treatment resulted in stable disease indicated by decreased tumor density and disappearance of some metastatic lesions lasting 15 months in a patient with lung adenocarcinoma harboring BRAF G469A and W604C (PMID: 30926357). 30926357
BRAF G464R Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G464R (PMID: 26343582). 26343582
BRAF N486_P490del BRAF R509H Advanced Solid Tumor sensitive GDC0879 Preclinical - Biochemical Actionable In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H Advanced Solid Tumor resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H BRAF V600E Advanced Solid Tumor resistant Vemurafenib Preclinical - Biochemical Actionable In a preclinical study, Zelboraf (vemurafenib) failed to reduce Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). 26996308
BRAF N486_P490del BRAF R509H BRAF V600E Advanced Solid Tumor sensitive GDC0879 Preclinical - Biochemical Actionable In a preclinical study, GDC0879 reduced Mek phosphorylation in transformed cells expressing BRAF N486_P490del, V600E, and R509H in culture (PMID: 26996308). 26996308
BRAF R509H BRAF V600E Advanced Solid Tumor sensitive 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 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 L485S BRAF V600E melanoma resistant Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, expression of BRAF L485S in melanoma cells harboring BRAF V600E conferred resistance to Tafinlar (dabrafenib) treatment in culture (PMID: 31925410). 31925410
BRAF N486_P490del melanoma sensitive Cobimetinib Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF N486_P490del demonstrated sensitivity to Cotellic (cobimetinib), resulting in decreased cell viability in culture (PMID: 26996308). 26996308
BRAF N486_P490del melanoma 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 AZ628 Preclinical - Cell culture Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del demonstrated sensitivity to AZ628, resulting in decreased cell viability and inhibition of Mek and Erk phosphorylation in culture (PMID: 26996308). 26996308
BRAF N486_P490del pancreatic ductal adenocarcinoma sensitive 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 Trametinib Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to Mekinist (trametinib), resulting in inhibition of cell growth in culture (PMID: 26732095). 26732095
BRAF N486_P490del pancreatic ductal adenocarcinoma predicted - sensitive 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 Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment resulted in partial response in a patient with pancreatic ductal adenocarcinoma harboring BRAF N486_P490del 8 weeks after initiation of treatment and lasted for 6 months (PMID: 29903880). 29903880
BRAF N486_P490del ovarian cancer 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 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 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 LY3009120 Preclinical Actionable In a preclinical study, an ovarian cancer cell line harboring BRAF N486_P490del was sensitive to LY3009120, resulting in inhibition of cell growth and decreased phosphorylation of MEK and ERK in culture (PMID: 26732095). 26732095
BRAF N486_P490del lymphatic system cancer predicted - sensitive Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) treatment in two patients with Langerhans cell histiocytosis harboring BRAF N486_P490del resulted in a complete response with no disease reactivation over 18 months of treatment in one patient and a partial response with stable disease in the lungs maintained over 12 months of treatment in a second patient (PMID: 32991018). 32991018
BRAF N486_P490del ovarian cancer predicted - sensitive 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 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 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 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 ovarian cancer sensitive 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 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 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 V504_R506dup Advanced Solid Tumor resistant 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 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 decreased response Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring BRAF G466E demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). 27523909
BRAF G466E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring BRAF G466E in culture (PMID: 27523909). 27523909
BRAF G466E melanoma 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 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 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 V600L mucosal melanoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Mekinist (trametinib) and Tafinlar (dabrafenib) combination treatment resulted in complete remission in a patient with unresectable hypopharyngeal mucosal melanoma harboring BRAF V600L (PMID: 35709404). 35709404
BRAF 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 V600E/K melanoma sensitive Dabrafenib + Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). detail... detail... 25399551
BRAF V600E/K melanoma sensitive Dabrafenib + Trametinib Phase II Actionable In a Phase II trial (S1320), intermittent dosing (3-week-off, 5-week-on) of Tafinlar (dabrafenib) and Mekinist (trametinib) did not improve median progression-free survival (5.5 v 9.0 months; HR=1.36, p=0.064, two-sided alpha=0.2) compared to continuous dosing in melanoma patients harboring BRAF V600E or V600K, and there were no significant differences in median overall survival, treatment response, or toxicity between the two treatment groups (PMID: 33020646; NCT02196181). 33020646
BRAF V600E/K melanoma sensitive Dabrafenib + Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (COMBI-AD) that supported FDA approval, adjuvant treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved estimated 3-year relapse-free survival rate (58% vs 39%, HR=0.47, P<0.001) and 3-year overall survival rate (86% vs 77%, HR=0.57; 95% CI, 0.42 to 0.79, P=0.0006) compared to placebo in stage III melanoma patients harboring BRAF V600E or V600K mutations (PMID: 28891408; NCT01682083). detail... 28891408 detail...
BRAF V600E/K melanoma predicted - sensitive Vemurafenib + XL888 Phase I Actionable In a Phase I trial, combined Zelboraf (vemurafenib) and XL888 treatment in patients with unresectable, BRAF inhibitor naive, metastatic melanoma harboring BRAF V600E (n=20) or V600K (n=1) resulted in complete and partial responses in 15% (3/20) and 60% (12/20) of evaluable patients, respectively, a 9.2-month median progression free survival, and a 34.6-month overall survival (PMID: 29674508). 29674508
BRAF V600E/K melanoma predicted - sensitive BGB-283 Case Reports/Case Series Actionable In a Phase I trial, Linfirafenib (BGB-283) treatment resulted in partial response in 15.1% (8/53) of solid tumor patients with BRAF mutations, including 5 of 23 patients with melanoma harboring BRAF V600E or V600K overall, and in the dose expansion phase 57.1% (4/7) patient with BRAF V600-mutant melanoma had a partial response (PMID: 32182156; NCT02610361). 32182156
BRAF V600E/K skin melanoma sensitive Binimetinib + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). 30959471 detail...
BRAF V600E/K skin melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) and Cotellic (cobimetinib) combination therapy is included in cutaneous melanoma guidelines for patients with metastatic or unresectable disease harboring a BRAF V600 activating mutation (NCCN.org). detail...
BRAF V600E/K melanoma sensitive Trametinib Phase I Actionable In a Phase I trial, Mekinist (trametinib) resulted in complete response in 7% (2/30), partial response in 33% (10/30), and stable disease in 37% (11/30) of BRAF-mutant melanoma patients (PMID: 22805292; NCT00687622). 22805292
BRAF V600E/K melanoma sensitive Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (METRIC) that supported FDA approval, Mekinist (trametinib) treatment, as compared to Deticine (dacarbazine) or Taxol (paclitaxel) treatment, resulted in improved progression-free survival of 4.8 months versus 1.5 months and an overall six month survival rate of 81% versus 67% in patients with BRAF V600E/K positive metastatic melanoma (PMID: 22663011; NCT01245062). 22663011 detail... detail...
BRAF V600E/K melanoma sensitive Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) resulted in a median overall survival (OS) of 33.6 months, a 1-year OS rate of 77.5%, and a 2-year OS rate of 57.7% in patients with advanced melanoma harboring BRAF V600E/K mutations compared to a median OS of 16.9 months and 1- and 2-year OS rates of 63.1% and 43.2%, respectively, in the Zelboraf (vemurafenib) treated group (PMID: 30219628; NCT01909453). detail... detail... detail... 30219628
BRAF V600E/K melanoma sensitive Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600E/K melanoma sensitive Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). detail... detail... 27480103
BRAF V600E/K PIK3CA wild-type melanoma sensitive Vemurafenib + ZSTK474 Preclinical Actionable In a preclinical study, ZSTK474 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + Vemurafenib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit Idelalisib Preclinical Actionable In a preclinical study, Zydelig (idelalisib) did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Selumetinib + ZSTK474 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and ZSTK474 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Dactolisib + Vemurafenib Preclinical Actionable In a preclinical study, BEZ235 and Zelboraf (vemurafenib) worked synergistically to inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit A66 Preclinical Actionable In a preclinical study, A66 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma no benefit TGX-221 Preclinical Actionable In a preclinical study, TGX-221 did not inhibit proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture (PMID: 26137449). 26137449
BRAF V600E/K PIK3CA wild-type melanoma sensitive Dactolisib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Koselugo (selumetinib) and BEZ235 combination treatment inhibited proliferation of melanoma cell lines harboring BRAF V600E/K and wild-type PIK3CA in culture, and synergistically inhibited tumor growth in cell line xenograft models (PMID: 26137449). 26137449
BRAF V600E/K PTEN loss Advanced Solid Tumor predicted - sensitive PX-866 + Vemurafenib Phase I Actionable In a Phase I trial, the combination therapy of PX-866 and Zelboraf (vemurafenib) demonstrated safety and resulted in an objective response in 28% (5/18) of advanced solid tumor patients harboring BRAF V600E or K, and of those five patients, 80% (4/5) also demonstrated loss of PTEN (PMID: 29051322). 29051322
BRAF V600E/K CDKN2A loss RB1 pos melanoma predicted - sensitive Palbociclib + Vemurafenib Phase Ib/II Actionable In a phase I/II trial, Ibrance (palbociclib) plus Zelboraf (vemurafenib) was safe and resulted in an overall response rate (ORR) of 26.7% (4/15), disease control rate (DCR) of 80% (12/15), and progression-free survival (PFS) of 2.8 mo in metastatic melanoma patients with prior BRAF inhibitor treatment and BRAF V600E/K, CDKN2A loss, and RB1 expression, and an ORR of 27.8% (5/18), DCR of 83.3% (10/18) and 2.8 mo PFS when combined with pts without prior BRAF inhibitor treatment (PMID: 33947696; NCT02202200). 33947696
BRAF 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 act mut colorectal cancer no benefit Venetoclax + VX-11e Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). 27974663
BRAF act mut Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). 24422853
BRAF act mut Advanced Solid Tumor sensitive Binimetinib + Encorafenib Phase Ib/II Actionable In a Phase Ib/II trial, Binimetinib (MEK162), in combination with Encorafenib (LGX818), demonstrated safety and efficacy in patients with BRAF mutant advanced solid tumors (J Clin Oncol 31, 2013 (suppl; abstr 9029)). detail...
BRAF act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating BRAF mutations were identified in 4 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
BRAF act mut colorectal cancer predicted - sensitive VX-11e + WEHI-539 Preclinical - Cell culture Actionable In a preclinical study, inhibition of Erk signaling by VX-11e sensitized colorectal cancer cell lines harboring KRAS or BRAF activating mutations to WEHI-539 in culture (PMID: 27974663). 27974663
BRAF act mut melanoma no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF act mut lung non-small cell carcinoma sensitive RAF709 Preclinical - Pdx Actionable In a preclinical study, RAF709 inhibited tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring BRAF activating mutations (PMID: 29343524). 29343524
BRAF act mut melanoma sensitive Cobimetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Cobimetinib (GDC-0973) induced cell death in human melanoma cell lines harboring BRAF activating mutations in culture and inhibited tumor growth in xenograft models (PMID: 22084396). 22084396
BRAF V600E BRAF over exp melanoma sensitive PLX8394 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced tumor growth in a Zelboraf (vemurafenib)-resistant cell line xenograft model of melanoma overexpressing BRAF V600E (PMID: 30559419). 30559419
BRAF V600E BRAF over exp melanoma resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, a cell line xenograft model of melanoma overexpressing BRAF V600E demonstrated resistance to Zelboraf (vemurafenib) treatment (PMID: 30559419). 30559419
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 K601E pancreatic endocrine carcinoma predicted - resistant Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a patient with a pancreatic neuroendocrine tumor harboring BRAF K601E demonstrated progressive disease when treated with a combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 31158244). 31158244
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, treatment of cells expressing BRAF K601E with the BRAF inhibitor, Zelboraf (vemurafenib), decreased activation of MEK and ERK (PMID: 22798288). 22798288
BRAF K601E Advanced Solid Tumor conflicting Vemurafenib 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 prostate adenocarcinoma no benefit 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 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 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 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 melanoma predicted - sensitive 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 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 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 lung adenocarcinoma predicted - sensitive 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 Cetuximab + Vemurafenib Preclinical - Pdx Actionable In a preclinical study, Erbitux (cetuximab) treatment in combination with Zelboraf (vemurafenib) did not inhibit Erk signaling or reduce tumor growth in a patient-derived xenograft (PDX) model of colorectal cancer harboring BRAF K601E (PMID: 30559419). 30559419
BRAF K601E melanoma predicted - sensitive 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 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 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 pancreatic endocrine carcinoma predicted - resistant 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 melanoma predicted - sensitive 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 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 Advanced Solid Tumor sensitive 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 MAP2K1 V211D colon cancer resistant Binimetinib Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer resistant Binimetinib + Cetuximab Preclinical - Pdx Actionable In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). 31227518
BRAF K601E MAP2K1 V211D colon cancer predicted - resistant 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 sensitive 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 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 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 G469A BRAF L584P melanoma predicted - sensitive 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 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 L597V lung adenocarcinoma resistant Ravoxertinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma 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 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 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 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 sensitive Dabrafenib + Trametinib Preclinical - Patient cell culture Actionable In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF L597V were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). 32540409
BRAF L597V lung adenocarcinoma resistant 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 endometrial adenocarcinoma no benefit 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 sensitive 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 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 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 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 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 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 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 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 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 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 V487_P492delinsA pancreatic cancer resistant Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, a human pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to treatment with Zelboraf (vemurafenib) in both culture and xenograft models (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer sensitive LY3009120 Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA were sensitive to LY3009120 in culture and in xenograft models, resulting in inhibition of tumor growth and partial tumor regression (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer resistant Dabrafenib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was resistant to Tafinlar (dabrafenib) (PMID: 26732095). 26732095
BRAF V487_P492delinsA pancreatic cancer sensitive Trametinib Preclinical Actionable In a preclinical study, a pancreatic cancer cell line harboring BRAF V487_P492delinsA was sensitive to Mekinist (trametinib) in culture, resulting in cell growth inhibition (PMID: 26732095). 26732095
BRAF 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 Binimetinib + Encorafenib Case Reports/Case Series Actionable In a clinical case study, a combination of Mektovi (binimetinib) and Braftovi (encorafenib) resulted in regression of lymphadenopathy, lung nodules, and subcutaneous nodules in a patient with metastatic melanoma harboring BRAF T599dup, and at 9 months from treatment initiation, a partial response was still observed (PMID: 35319964). 35319964
BRAF T599dup melanoma predicted - sensitive 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 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 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 T310I 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 T310I in culture (PMID: 31158244). 31158244
BRAF L485W gallbladder cancer sensitive Ulixertinib Case Reports/Case Series Actionable In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a complete response lasting almost 1 year in a gallbladder cancer patient harboring BRAF L485W (PMID: 29247016, PMID: 29247021). 29247021 29247016
BRAF 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 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 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 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 V600E thyroid gland papillary carcinoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). detail...
BRAF V600E thyroid gland papillary carcinoma sensitive Dabrafenib Clinical Study - Cohort Actionable In a clinical study, Tafinlar (dabrafenib) treatment stimulated radioiodine uptake in 60% (6/10) of patients with metastatic iodine-refractory papillary thyroid cancer harboring BRAF V600E (PMID: 25549723; NCT01534897). 25549723
BRAF V600E endometrial adenocarcinoma predicted - sensitive Dabrafenib + Rabeprazole + Rifampin Case Reports/Case Series Actionable In a Phase I trial, combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, that recurred 11 years after original diagnosis and was refractory to treatment with chemotherapy, led to reduction of lung metastases and pelvic tissue mass at three months, but a slight increase in pelvic mass was observed at six months (PMID: 33537843; NCT01954043). 33537843
BRAF V600E melanoma sensitive SBI-0640756 Preclinical Actionable In a preclinical study, SBI-0640756 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma sensitive Saracatinib Preclinical Actionable In a preclinical study, saracatinib inhibited proliferation of human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture (PMID: 23242808). 23242808
BRAF V600E Advanced Solid Tumor sensitive SB590885 Preclinical Actionable In a preclinical study, SB590885 inhibited inhibited Erk phosphorylation and cell proliferation of transformed cells expression BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E hairy cell leukemia predicted - sensitive Ruxolitinib + Vemurafenib Phase II Actionable In a Phase II trial (HCL-PG03), combined Zelboraf (vemurafenib) and Jakafi (ruxolitinib) therapy in relapsed or refractory hairy cell leukemia patients with BRAF V600E demonstrated safety, and led to complete response (CR) in 87% (26/30) of patients, including 17 (65%) with negative minimal residual disease, a progression-free survival rate of 78% at a median follow-up of 37 months, and a relapse-free survival rate of 85% in the 26 patients with a CR at a median follow-up of 34 months (PMID: 33979489). 33979489
BRAF V600E colorectal cancer sensitive 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 lung cancer sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a partial response in two patients with lung cancer each harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E melanoma sensitive Encorafenib + Ribociclib Phase Ib/II Actionable In a Phase Ib/II trial, Encorafenib (LGX818) and Kisqali (ribociclib) combination treatment resulted in confirmed partial response in 7.1% (2/28), unconfirmed partial response in 10.7% (3/28), and stable disease in 35.7% (10/28) of patients with melanoma harboring BRAF V600E (PMID: 28351928). 28351928
BRAF V600E melanoma sensitive SBI-0640756 + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) in combination with SBI-0640756 inhibited the association of eIF4G1 and eIF4E in Zelboraf (vemurafenib) resistant human melanoma cell lines harboring BRAF V600E in culture and reduced tumor growth in xenograft models (PMID: 26603897). 26603897
BRAF V600E colorectal cancer sensitive BI 882370 + Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring BRAF V600E were sensitive to the combination of BI 882370 and Mekinist (trametinib) in xenograft models, resulting in tumor growth inhibition and partial tumor regression (PMID: 26916115). 26916115
BRAF V600E colorectal cancer 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 colorectal cancer sensitive Regorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Stivarga (regorafenib) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture and suppressed angiogenesis and tumor growth in cell line xenograft models (PMID: 21170960). 21170960
BRAF V600E colon adenocarcinoma predicted - sensitive 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 colorectal cancer sensitive PD-0325901 Preclinical Actionable In a preclinical study, PD-0325901 inhibited growth of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E 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 pleomorphic xanthoastrocytoma sensitive 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 hairy cell leukemia not applicable N/A Guideline Diagnostic BRAF V600E is diagnostic and aids in distinguishing classic hairy cell leukemia (cHCL) from variant hairy cell leukemia (HCLv) and other B-cell lymphomas and leukemias (PMID: 29118233, NCCN.org). detail... 29118233
BRAF V600E colorectal cancer no benefit Panitumumab + Trametinib Phase I Actionable In a Phase I trial, combination therapy consisting of Vectibix (panitumumab) and Mekinist (trametinib) resulted in an overall response rate of 0% (0/31), stable disease in 55% (17/31), and a median progression-free survival of 2.6 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E Advanced Solid Tumor no benefit 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 colorectal cancer sensitive 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 endometrial adenocarcinoma predicted - sensitive Dabrafenib + Rabeprazole + Rifampin + Trametinib Case Reports/Case Series Actionable In a Phase I trial, the addition of Mekinist (trametinib) to the combination treatment with Tafinlar (dabrafenib), Rabeprazol, and Rifampin resulted in a maintained radiographic response of lung metastases and stable pelvic mass size in a patient with metastatic endometrial adenocarcinoma harboring BRAF V600E, which lasted for 12 months (PMID: 33537843; NCT01954043). 33537843
BRAF V600E melanoma sensitive SBI-0640726 Preclinical Actionable In a preclinical study, SBI-0640726 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E colorectal cancer sensitive 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 cancer sensitive Ponatinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) and Zelboraf (vemurafenib) treatment synergistically inhibited proliferation of thyroid cancer cells harboring BRAF V600E in culture (PMID: 31937621). 31937621
BRAF V600E melanoma sensitive Dabrafenib + 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 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 ovarian cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 50% (2/4, 2 partial response) in patients with ovarian cancer harboring BRAF V600E, and stable disease lasting more than 120 days in 1 patient (PMID: 29320312; NCT02091141). 29320312
BRAF V600E ovarian cancer predicted - sensitive Vemurafenib Phase II Actionable In a Phase II trial (VE-BASKET), responses were seen in ovarian cancer patients harboring BRAF V600E (n=4) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E 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 adenocarcinoma predicted - sensitive 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 colorectal cancer sensitive 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 skin melanoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E pancreatic ductal adenocarcinoma predicted - sensitive 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 thyroid gland cancer sensitive CLM3 Preclinical Actionable In a preclinical study, CLM3 inhibited growth, Egfr signaling, and CCND1 expression in thyroid cancer cells harboring BRAF V600E in culture (PMID: 24423321). 24423321
BRAF V600E colon cancer sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of colon cancer cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E melanoma sensitive AZ628 Preclinical - Cell culture Actionable In a preclinical study, AZ628 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E childhood pilocytic astrocytoma predicted - sensitive Selumetinib Phase I Actionable In a Phase I trial, Koselugo (selumetinib) treatment resulted in a sustained partial response (PR) in 36% (9/25) and stable disease in 36% (9/25) of pediatric patients with pilocytic astrocytoma harboring KIAA1549-BRAF (n=18) or BRAF V600E (n=7), with a 2-year progression-free survival of 70%, and 29% (2/7) of the patients harboring BRAF V600E achieved PR (PMID: 31151904; NCT01089101). 31151904
BRAF V600E high grade glioma predicted - sensitive Everolimus + PLX4720 Preclinical - Cell culture Actionable In a preclinical study, Afinitor (everolimus) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture (PMID: 27217440). 27217440
BRAF V600E melanoma 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 pilocytic astrocytoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with pilocytic astrrocytoma harboring BRAF V600E who stayed on treatment for 15.3 months (PMID: 30351999; NCT01524978). 30351999
BRAF V600E colorectal cancer predicted - sensitive Dabrafenib + Panitumumab + Trametinib Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib), Vectibix (panitumumab), and Mekinist (trametinib) resulted in an overall response rate of 21% (19/91, 1 complete response, 18 partial response), stable disease in 65% (59/91), and a median progression-free survival of 4.2 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E sarcoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), responses were seen in sarcoma patients harboring BRAF V600E (n=6) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 1 patient with a partial response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E 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 anaplastic pleomorphic xanthoastrocytoma predicted - sensitive 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 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 anaplastic astrocytoma sensitive Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic astrocytoma (NCCN.org). detail...
BRAF V600E glioblastoma decreased response 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 lymphatic system cancer predicted - sensitive 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 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 melanoma sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in melanoma cell lines harboring BRAF V600E in culture (PMID: 26208524). 26208524
BRAF V600E Advanced Solid Tumor sensitive CI-1040 Preclinical Actionable In a preclinical study, CI-1040 (PD184352) inhibited Erk phosphorylation and growth of transformed cells expressing BRAF V600E in culture (PMID: 20538618). 20538618
BRAF V600E melanoma sensitive Alpelisib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alpelisib (BYL719) and PLX4720 enhanced antitumor activity in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models, and decreased Akt signaling in culture (PMID: 27924459). 27924459
BRAF V600E melanoma sensitive INU-152 Preclinical - Cell line xenograft Actionable In a preclinical study, INU-152 reduced MEK and ERK phosphorylation and growth of a melanona cell line harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models (PMID: 28645859). 28645859
BRAF V600E colorectal cancer sensitive BGB-283 Preclinical - Pdx & cell culture Actionable In a preclinical study, BGB-283 inhibited Braf phosphorylation and cell proliferation in colorectal cancer cell lines harboring BRAF V600E in culture, and resulted in partial tumor regression in both cell line and patient-derived xenograft models (PMID: 26208524). 26208524
BRAF V600E colorectal cancer predicted - sensitive LSN3074753 Preclinical - Pdx Actionable In a preclinical study, LSN3074753 demonstrated modest efficacy in patient-derived xenograft models of colorectal cancer harboring BRAF V600E, resulted in tumor growth inhibition or regression, but relapse upon discontinuation of treatment (PMID: 28611205). 28611205
BRAF V600E melanoma sensitive 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 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 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 pleomorphic xanthoastrocytoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a complete intracranial response 2 months after treatment in a patient with anaplastic pleomorphic xanthoastrocytoma harboring BRAF V600E, although the disease progressed 1 month later (PMID: 31386052). 31386052
BRAF V600E pleomorphic xanthoastrocytoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 42.9% (3/7, 1 complete response, 2 partial responses) and a clinical benefit rate of 57% in patients with pleomorphic xanthoastrocytoma harboring BRAF V600E, with a median progression-free survival of 5.7 months, and median overall survival not reached (PMID: 30351999; NCT01524978). 30351999
BRAF V600E colorectal cancer sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma sensitive AZD0364 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD0364 (ATG-017) inhibited cell growth, decreased phosphorylation of Erk target genes, and increased expression of apoptosis markers in melanoma cells harboring BRAF V600E in culture, and resulted in tumor regression in cell line xenograft models (PMID: 33273059). 33273059
BRAF V600E melanoma sensitive Selumetinib Phase II Actionable In a Phase II trial, a favorable response rate to selumetinib (AZD6244) was observed in mutant BRAF but not BRAF wild-type melanoma patients (PMID: 22048237). 22048237
BRAF V600E ovarian serous carcinoma predicted - sensitive BGB-283 Case Reports/Case Series Actionable In a Phase I trial, Lifirafenib (BGB-283) treatment demonstrated safety and resulted in partial response (PR) in 15.1% (8/53) of advanced solid tumor patients harboring a BRAF mutation, including 1 patient with BRAF V600E-mutant low-grade serous ovarian cancer (PMID: 32182156; NCT02610361). 32182156
BRAF V600E melanoma sensitive Imatinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Gleevec (imatinib) and PLX4720 enhanced antitumor efficacy of melanoma cells harboring BRAF V600E, demonstrating decreased cell survival in xenograft models, and decreased phosphorylation of Mapk1 in culture (PMID: 27924459). 27924459
BRAF V600E colon cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab), as a monotherapy, is not indicated for use in colon cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive Dabrafenib + Panitumumab Phase I Actionable In a Phase I trial, combination therapy consisting of Tafinlar (dabrafenib) and Vectibix (panitumumab) resulted in an overall response rate of 10% (2/20, 1 complete response, 1 partial response), stable disease in 80% (16/20), and a median progression-free survival of 3.5 months in patients with BRAF V600E colorectal cancer (PMID: 29431699; NCT01750918). 29431699
BRAF V600E colorectal cancer sensitive Dabrafenib + Panitumumab Phase Ib/II Actionable In a Phase Ib/II trial, treatment with the combination of Vectibix (panitumumab) and Tafinlar (dabrafenib) resulted in stable disease in 7/8 colorectal cancer patients harboring a BRAF V600E mutation (J Clin Oncol 32:5s, 2014 (suppl; abstr 3515)). detail...
BRAF V600E colorectal cancer predicted - sensitive 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 predicted - sensitive 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 pancreatic endocrine carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a patient with pancreatic endocrine carcinoma found to harbor BRAF V600E demonstrated stable disease and some tumor shrinkage when treated with Zelboraf (vemurafenib) (PMID: 31158244). 31158244
BRAF V600E colorectal cancer sensitive PLX4720 + TAK-632 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 and TAK-632 combination treatment resulted in durable inhibition of Erk signaling and tumor growth in xenograft models of colorectal cancer cells harboring BRAF V600E (PMID: 27523909). 27523909
BRAF V600E 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 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 thyroid gland cancer sensitive PLX4720 + Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) and PLX4720 treatment demonstrated synergy, and inhibited Erk, Mek, and c-jun phosphorylation, reduced cell proliferation, colony formation, and migration, and induced apoptosis in thyroid cancer cells harboring BRAF V600E and in PLX4720-resistant cells harboring BRAF V600E in culture, and inhibited tumor growth, reduced lung and liver metastases, and increased survival in cell line xenograft models (PMID: 31937621). 31937621
BRAF V600E high grade glioma predicted - sensitive Vemurafenib + ZM336372 Preclinical - Patient cell culture Actionable In a preclinical study, combination treatment with Zelboraf (vemurafenib) and ZM336372 treatment led to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). 34433654
BRAF V600E melanoma sensitive PAC-1 + Trametinib + Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, the addition of PAC-1 to Mekinist (trametinib) and Zelboraf (vemurafenib) led to greater levels of caspase-3 activity and apoptosis in melanoma cells harboring BRAF V600E when compared to Zelboraf (vemurafenib) and Mekinist (trametinib) treatment without PAC-1 (PMID: 27297867). 27297867
BRAF V600E 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 lung papillary adenocarcinoma predicted - sensitive 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 sensitive 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 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 (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 Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E achieved an overall response rate of 54% (13/24, 2 complete responses, 11 partial responses, and 10 with stable disease) and a disease control rate of 96% following treatment with Zelboraf (vemurafenib) (PMID: 26200454). 26200454
BRAF V600E lung non-small cell carcinoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations who can not tolerate the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) (NCCN.org). detail...
BRAF V600E lung non-small cell carcinoma sensitive Vemurafenib Phase II Actionable In a Phase II trial (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 colorectal cancer sensitive Cetuximab + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (BEACON CRC) trial that supported FDA approval, Braftovi (encorafenib) and Erbitux (cetuximab) combination treatment (n=113) resulted in improved median overall survival (8.4 vs 5.4 months, HR=0.60, p<0.001), confirmed response rate (20% vs 2%, p<0.001), and median progression-free survival (4.2 vs 1.5 months, HR=0.40, p<0.001) compared to control (n=107) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 31566309; NCT02928224). detail... 31566309
BRAF V600E colorectal cancer sensitive Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Encorafenib (LGX818) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive GSK2126458 + Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E melanoma sensitive 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 no benefit Sorafenib Phase II Actionable In a Phase II study, Nexavar (sorafenib) displayed negligible efficacy in melanoma patients with BRAF V600E mutations (PMID: 16880785, PMID: 22394203). 22394203 16880785
BRAF V600E melanoma predicted - sensitive 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 melanoma sensitive Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E melanoma predicted - sensitive LXH 254 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E was sensitive to treatment with LXH254, demonstrating inhibition of cell proliferation in culture, and inhibition of tumor growth and tumor regression in a cell line xenograft model of melanoma (PMID: 33355204). 33355204
BRAF V600E neuroendocrine carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), responses were seen in patients with neuroendocrine carcinoma harboring BRAF V600E (n=3) when treated with Zelboraf (vemurafenib), including 1 patient with a partial response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E melanoma no benefit Palbociclib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with Ibrance (palbociclib) in a melanoma cell line xenograft model harboring BRAF V600E resulted in no benefit, demonstrating low but continuous growth (PMID: 27488531). 27488531
BRAF V600E Advanced Solid Tumor sensitive PLX8394 Preclinical Actionable In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF V600E splice variants (PMID: 24422853). 24422853
BRAF V600E high grade glioma no benefit ZM336372 Preclinical - Patient cell culture Actionable In a preclinical study, ZM336372 treatment did not lead to inhibition of cell growth in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). 34433654
BRAF V600E colorectal 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 pleomorphic xanthoastrocytoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with pleomorphic xanthoastrocytoma achieved a partial response lasting 7.2 months (PMID: 32758030; NCT02465060). 32758030
BRAF V600E colorectal cancer sensitive Cetuximab + Irinotecan + Vemurafenib Phase II Actionable In a Phase II trial (SWOG1406), addition of Zelboraf (vemurafenib) to Camptosar (irinotecan) plus Erbitux (cetuximab) improved progression-free survival (4.4 vs. 2.0 mo, HR 0.50, p=0.001), response rate (17% vs 4%, p=0.05), and disease control rate (67% vs. 22%, p<0.001) in patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 33356422; NCT02164916). 33356422
BRAF V600E colorectal cancer sensitive Cetuximab + Irinotecan + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Erbitux (cetuximab) and Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). 22180495
BRAF V600E 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 lung non-small cell carcinoma sensitive 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 Dabrafenib + Trametinib Guideline Actionable Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is in guidelines for metastatic non-small cell lung cancer patients with BRAF V600E mutations (NCCN.org). detail...
BRAF V600E melanoma 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 triple-receptor negative breast cancer predicted - sensitive Nab-paclitaxel + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) and Abraxane (nab-paclitaxel) combination treatment resulted in regression of some metastatic pulmonary lesions and a progression-free survival of 4.4 months in a patient with triple-negative breast cancer harboring BRAF V600E, but a biopsy in lesions that progressed showed acquisition of additional mutations in PDGFRB, NF2, GRM3, MLH1, FOXA1, LRP1B, and AR amplification (PMID: 34818649). 34818649
BRAF V600E salivary gland carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II (MyPathway) trial, Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with advanced salivary gland carcinoma harboring BRAF V600E, with a progression-free survival of 18.5 months (PMID: 32067683; NCT02091141). 32067683
BRAF V600E melanoma sensitive BI 882370 + Trametinib Preclinical Actionable In a preclinical study, xenograft models of melanoma harboring BRAF V600E treated with the combination of BI 882370 and Mekinist (trametinib) demonstrated tumor regression with no regrowth during the 5 weeks of treatment (PMID: 26916115). 26916115
BRAF V600E colorectal cancer sensitive ERAS-007 Preclinical - Pdx & cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited cell proliferation and Erk signaling in colorectal cancer cell lines harboring BRAF V600E in culture, and induced tumor regression in two patient-derived xenograft (PDX) models (PMID: 34337566). 34337566
BRAF V600E melanoma sensitive 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 pancreatic ductal adenocarcinoma predicted - sensitive 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 melanoma no benefit RM-018 Preclinical - Cell culture Actionable In a preclinical study, RM-018 did not inhibit growth of melanoma cells harboring BRAF V600E in culture (PMID: 33824136). 33824136
BRAF V600E melanoma decreased response Pembrolizumab Clinical Study Actionable In a retrospective analysis, patients with melanoma harboring BRAF V600E (n=84) had decreased response rates (29% vs. 53%, p=0.059), progression-free survival (2.7 vs. 19 months, p=0.049), and overall survival (11.7 vs. 20.4 months, p=0.081) relative to patients with BRAF V600K (n=19) when treated with Keytruda (pembrolizumab) (n=62 and 17 for BRAF V600E and V600K, respectively) or Opdivo (nivolumab) (n=22 and 2 for BRAF V600E and V600K, respectively) (PMID: 30630828). 30630828
BRAF V600E melanoma conflicting PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E melanoma conflicting PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, a melanoma cell line xenograft model harboring BRAF V600E treated with PD-0325901 demonstrated stable tumor growth, but by day 44, growth ensued and thus, demonstrated no benefit (PMID: 27488531). 27488531
BRAF V600E 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 glioblastoma sensitive 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 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 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 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 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 glioblastoma sensitive 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 melanoma sensitive Erlotinib + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Tarceva (erlotinib) resulted in antitumor efficacy in a melanoma cell line harboring BRAF V600E, demonstrating decreased cell survival and increased apoptotic activity in xenograft models and culture (PMID: 27924459). 27924459
BRAF V600E melanoma 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 sensitive 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 Ganetespib + TAK-733 Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor, Ganetespib, in combination with the MEK1/2 inhibitor TAK-733, caused the regression of tumors in vemurafenib-resistant cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E colorectal cancer predicted - sensitive LY3214996 Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line harboring BRAF V600E and NF1 T2805I was sensitive to treatment with LY3214996 in culture, demonstrating decreased cell viability (PMID: 31744895). 31744895
BRAF V600E 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 melanoma sensitive GDC0879 Preclinical - Pdx & cell culture Actionable In a preclinical study, GDC0879 inhibited survival of melanoma cell lines harboring BRAF V600E in cell culture, cell line xenograft and patient-derived xenograft (PDX) models (PMID: 19276360). 19276360
BRAF V600E colorectal cancer sensitive 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 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 IDH-wildtype glioblastoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in disease stability over 15 months in a patient with epithelioid glioblastoma harboring BRAF V600E, who previously progressed on conventional treatment options (PMID: 34232949). 34232949
BRAF V600E thyroid gland cancer sensitive Dasatinib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and SCH772984 synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E skin melanoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) therapy is included in guidelines for cutaneous melanoma patients with unresectable or metastatic disease harboring BRAF V600 activating mutations, such as BRAF V600E, in cases where BRAF/MEK inhibitor combination therapy is contraindicated (NCCN.org). detail...
BRAF V600E brain glioblastoma multiforme predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in tumor shrinkage after 2 months in a patient with epithelioid glioblastoma multiforme harboring BRAF V600E, who had progressed after resection, radiotherapy, and chemotherapy, and following an interruption in therapy due to toxicity demonstrated a partial response and remained progression-free for 19 months, prior to progressing 29 months after initiation of therapy (PMID: 33461766). 33461766
BRAF V600E 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 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 intrahepatic cholangiocarcinoma predicted - sensitive 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 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 histiocytic and dendritic cell cancer predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), responses were seen in patients with histiocytic neoplasms harboring BRAF V600E (n=27) when treated with Zelboraf (vemurafenib), including 15 patients with a partial response and 2 patients with a complete response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E 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 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 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 Advanced Solid Tumor predicted - sensitive 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 thyroid gland cancer sensitive Lapatinib + Vemurafenib Preclinical Actionable In a preclinical study, the combination of Tykerb (lapatinib) and Zelboraf (vemurafenib) inhibited growth of thyroid cancer cells harboring a BRAF V600E mutation in culture and in BRAF-mutant mouse models of thyroid cancer (PMID: 23365119). 23365119
BRAF V600E 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 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 melanoma predicted - sensitive U0126 Preclinical - Cell culture Actionable In a preclinical study, U0126 treatment inhibited Erk phosphorylation and reduced growth of melanoma cells harboring BRAF V600E in culture (PMID: 18794803). 18794803
BRAF V600E 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 biliary tract cancer sensitive Dabrafenib + Trametinib Phase II Actionable In a Phase II trial (ROAR), Tafinlar (dabrafenib) in combination with Mekinist (trametinib) demonstrated a manageable safety profile and resulted in an overall response rate of 51% (22/43, all partial responses) in patients with biliary tract cancer harboring BRAF V600E, with a median duration of response of 9 months, a median progression-free survival of 9 months, and a median overall survival of 14 months (PMID: 32818466; NCT02034110). 32818466
BRAF V600E biliary tract cancer sensitive Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) in combination with Mekinist (trametinib) is included in guidelines as subsequent-line therapy for patients with biliary tract cancer harboring BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive Irinotecan + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Camptosar (irinotecan) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). 22180495
BRAF V600E melanoma sensitive RO4987655 Preclinical - Cell culture Actionable In a preclinical study, RO4987655 inhibited proliferation of melanoma cells harboring BRAF V600E in culture (PMID: 26438159). 26438159
BRAF V600E melanoma sensitive 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 skin melanoma sensitive Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the Hsp90 inhibitor Ganetespib destabilized BRAF, especially BRAF V600E, resulted in loss of cell viability in culture and antitumor effects in cell line xenograft models of melanoma (PMID: 24398428). 24398428
BRAF V600E melanoma sensitive PLX4720 + Selumetinib Preclinical Actionable In a preclinical study, PLX4720 and Selumetinib (AZD6244) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E melanoma predicted - sensitive RAF265 Phase I Actionable In a Phase I trial, treatment with RAF265 in melanoma patients resulted in an objective response rate of 12.1% (8/66), including a partial response in four patients harboring BRAF V600E, two partial responses and one complete response in patients with wild-type BRAF, and one complete response in a patient with unknown mutational status (PMID: 28719152). 28719152
BRAF V600E melanoma sensitive 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 colon cancer sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive Dabrafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Tafinlar (dabrafenib) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E Advanced Solid Tumor predicted - sensitive PF-00477736 + PF3644022 Preclinical - Cell culture Actionable In a preclinical study, Chk1 inhibitor PF-477736 and MK2 inhibitor PF3644022 synergistically inhibited growth of transformed cells over expressing BRAF V600E in culture, while single agent inhibition had no effect (PMID: 26140595). 26140595
BRAF V600E 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 lung non-small cell carcinoma not predictive Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). 29723688
BRAF V600E melanoma sensitive PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, PLX4720 inhibited growth of melanoma cells harboring BRAF V600E in culture and in cell line xenograft models (PMID: 18287029). 18287029
BRAF V600E colorectal cancer sensitive Panitumumab + Vemurafenib Phase I Actionable In a Phase I trial, 83% (10/12) of patients with colorectal cancer carrying a BRAF V600E mutation demonstrated tumor regression when treated with a combination of Zelboraf (vemurafenib) and Vectibix (panitumumab) (PMID: 25589621). 25589621
BRAF V600E peritoneal serous papillary adenocarcinoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with mucinous-papillary serous adenocarcinoma of the peritoneum achieved a partial response (PMID: 32758030; NCT02465060). 32758030
BRAF V600E melanoma sensitive CCT196969 Preclinical - Pdx Actionable In a preclinical study, CCT196969 inhibited growth of a human melanoma cell line harboring BRAF V600E in culture, and induced tumor regression in several BRAF V600E-mutant melanoma patient-derived xenograft models (PMID: 25500121). 25500121
BRAF V600E hairy cell leukemia sensitive Dabrafenib + Trametinib Phase II Actionable In a Phase II trial (ROAR), the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) was well tolerated and resulted in an overall response rate of 78% (32/41; 20 complete responses, 12 partial responses) in patients with heavily pretreated recurrent/refractory hairy cell leukemia harboring BRAF V600E, with a 12-month progression-free-survival and overall survival rates of 97.6% and 97.6%, respectively (Blood (2018) 132 (Supplement 1): 391; NCT02034110). detail...
BRAF V600E thyroid gland papillary carcinoma sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in a complete or partial response in three papillary thyroid carcinoma patients harboring BRAF V600E, with one patient having a response that lasted for 8 months who remained progression-free for 12 months, and another two patients having a stable disease that lasted for 11 and 13 months, respectively (PMID: 20818844; NCT00215605). 20818844
BRAF V600E thyroid gland papillary carcinoma sensitive Vemurafenib Phase II Actionable In a Phase II trial, Zelboraf (vemurafenib) treatment resulted in a partial response in 38.5% (10/26) of patients with metastatic or unresectable, radioactive iodine-refractory papillary thyroid carcinoma harboring BRAF V600E that were multikinase inhibitor-naive, with a disease control rate of 73%, and a median progression-free survival of 18.2 months (PMID: 27460442; NCT01286753). 27460442
BRAF V600E thyroid gland papillary carcinoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid papillary carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). detail...
BRAF V600E thyroid gland cancer sensitive Dasatinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Sprycel (dasatinib) and Koselugo (selumetinib) synergistically inhibited proliferation and induced apoptosis in both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive PLX8394 Preclinical - Cell culture Actionable In a preclinical study, PLX8394 treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). 30559419
BRAF V600E colon neuroendocrine neoplasm no benefit Binimetinib Case Reports/Case Series Actionable In Phase II trial, Mektovi (binimetinib) therapy in a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation who had previously progressed on Tafinlar (dabrafinib) resulted in disease progression after two cycles (PMID: 30181415; NCT01885195). 30181415
BRAF V600E glioblastoma sensitive Ulixertinib Phase I Actionable In a Phase I trial, treatment with BVD-523 (Ulixertinib) resulted in a partial response in a patient with glioblastoma harboring BRAF V600E (PMID: 29247021). 29247021
BRAF V600E colorectal cancer sensitive Cetuximab + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of PLX4720 and Erbitux (cetuximab) inhibited tumor growth in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 22281684). 22281684
BRAF V600E anaplastic astrocytoma 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 glioblastoma decreased response PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, a glioblastoma cell line harboring BRAF V600E demonstrated a decreased response to treatment with PD-0325901, demonstrating increased viability of CD133 positive cells in culture (PMID: 26573800). 26573800
BRAF V600E pleomorphic xanthoastrocytoma sensitive 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 pleomorphic xanthoastrocytoma sensitive 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 ganglioglioma predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in partial response 8 weeks after therapy initiation in a pediatric patient with anaplastic ganglioglioma harboring BRAF V600E, but disease progression occurred at 40 weeks due to acquired resistance (PMID: 29880583). 29880583
BRAF V600E melanoma sensitive Vemurafenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (BRIM-3) that supported FDA approval, Zelboraf (vemurafenib), as compared to Deticene (dacarbazine), resulted in an improved overall survival (OS) (13.6 vs 9.7 months, HR=0.81, p=0.03) in patients with BRAF V600E-positive metastatic melanoma, with estimated OS rates of 56%, 30%, 21%, and 17% at 1, 2, 3, and 4 years, respectively (PMID: 28961848, PMID: 21639808; NCT01006980), and BRAF V600E is included on the companion diagnostic (FDA.gov). 28961848 detail... detail... 21639808
BRAF V600E melanoma sensitive Vemurafenib Phase I Actionable In a Phase I trial, Zelboraf (vemurafenib) treatment resulted in an overall response rate of 81% (26/32; 2 complete 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 colorectal cancer sensitive BGB-283 + Cetuximab Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-283 in combination with Erbitux (cetuximab) demonstrated enhanced tumor suppression in colorectal cancer cell line xenograft models harboring BRAF V600E (PMID: 26208524). 26208524
BRAF V600E colon neuroendocrine neoplasm predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafinib) treatment of a patient with recurrent neuroendocrine carcinoma of the colon harboring a BRAF V600E mutation resulted in stable disease for 6 months before disease progression (PMID: 30181415). 30181415
BRAF V600E melanoma sensitive PLX4720 + Tivozanib Preclinical Actionable In a preclinical study, PLX4720 and Tivozanib (AV-951) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E pancreatic ductal adenocarcinoma predicted - sensitive Trametinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) and Mekinist (trametinib) combination treatment resulted in decreased tumor markers in a patient with pancreatic ductal adenocarcinoma harboring BRAF V600E, as well as a germline ATM mutation, and the patient received 13 months of combination therapy and was followed for 24 months (PMID: 35145907). 35145907
BRAF V600E colorectal cancer sensitive 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 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 melanoma sensitive Encorafenib Preclinical - Cell culture Actionable In a preclinical study, Braftovi (encorafenib) treatment inhibited Erk phosphorylation and reduced proliferation of melanoma cells harboring monomeric BRAF V600E in culture (PMID: 30559419). 30559419
BRAF V600E melanoma sensitive Encorafenib Preclinical - Cell line xenograft Actionable In preclinical studies, Encorafenib (LGX818) treatment of human melanoma xenograft models with BRAF V600E significantly decreased Mek activation and resulted in tumor regression (Cancer Res: 72(8) Suppl 1, Abstract #3790). detail...
BRAF V600E melanoma sensitive 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 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 DETD-35 Preclinical - Cell line xenograft Actionable In a preclinical study, DETD-35 inhibited proliferation and colony formation of melanoma cells harboring BRAF V600E in culture and reduced tumor size in xenograft models (PMID: 27048951). 27048951
BRAF V600E colorectal cancer sensitive Cetuximab + Dabrafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and Tafinlar (dabrafenib) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E colorectal cancer sensitive CCT196969 Preclinical - Cell culture Actionable In a preclinical study, CCT196969 inhibited growth of BRAF-mutant colorectal cancer cell lines in culture (PMID: 25500121), which have been reported to harbor BRAF V600E (PMID: 15294323). 25500121 15294323
BRAF V600E colorectal cancer sensitive Erlotinib + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment in combination with Tarceva (erlotinib) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E compared to either agent alone (PMID: 22180495). 22180495
BRAF V600E colorectal cancer sensitive Erlotinib + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zelboraf (vemurafenib) and Tarceva (erlotinib) resulted in improved inhibition of tumor growth in BRAF V600E mutant human colon cancer cell line xenograft models compared to either drug as monotherapy (PMID: 22448344). 22448344
BRAF V600E melanoma sensitive TW-37 + Vemurafenib Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colon cancer sensitive Cetuximab + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Erbitux (cetuximab) is included in guidelines as primary or subsequent therapy for patients with colon cancer harboring BRAF V600E (NCCN.org). detail...
BRAF V600E 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 colorectal cancer no benefit Vemurafenib Phase II Actionable In a Phase II trial, Zelboraf (vemurafenib) did not demonstrate meaningful clinical activity as a single agent, resulted in partial response in 5% (1/21) and stable disease in 33% (7/21) of patients with metastatic colorectal cancer harboring BRAF V600E (PMID: 26460303; NCT00405587). 26460303
BRAF V600E colorectal cancer no benefit Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, colorectal cancer cell lines were not sensitive to growth inhibition by Zelboraf (vemurafenib) in culture or xenograft models, due to feedback activation of EGFR signaling (PMID: 22281684). 22281684
BRAF V600E colorectal cancer 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 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 pilocytic astrocytoma sensitive Selumetinib Guideline Actionable Koselugo (selumetinib) is included in guidelines for patients with recurrent or progressive pilocytic astrocytoma harboring BRAF V600E (NCCN.org). detail...
BRAF V600E pilocytic astrocytoma sensitive Dabrafenib + Trametinib Guideline Actionable Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines as an adjuvant treatment for patients with pilocytic astrocytoma harboring BRAF V600E (NCCN.org). detail...
BRAF V600E 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 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 Case Reports/Case Series Actionable In a clinical case study, the combination of Zelboraf (vemurafenib) and Erbitux (cetuximab) was tolerated and showed clinical benefit in a patient with BRAF V600E mutant colorectal cancer (PMID: 24523613). 24523613
BRAF V600E colorectal cancer sensitive Cetuximab + Vemurafenib Preclinical - Cell 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 rectum cancer resistant Cetuximab Guideline Actionable Erbitux (cetuximab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer sensitive Cetuximab + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab) and SCH772984 inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E thyroid gland cancer sensitive 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 sensitive 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 histiocytic sarcoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, 1 patient with histiocytic sarcoma of the brain achieved a partial response with an ongoing progression-free survival at 20.9 months (PMID: 32758030; NCT02465060). 32758030
BRAF V600E melanoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited cell invasion, cell signaling, and proliferation in human melanoma cell lines harboring BRAF V600E that are resistant to Braf inhibition in culture and in animal models (PMID: 23242808). 23242808
BRAF V600E colorectal cancer sensitive Dabrafenib + Regorafenib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in colorectal cancer cell lines harboring BRAF V600E resulted in suppression of colony formation in culture, and inhibition of tumor growth in a cell line xenograft model (PMID: 33568355). 33568355
BRAF V600E neuroendocrine tumor predicted - sensitive 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 thyroid gland cancer predicted - sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E melanoma sensitive Cediranib + PLX4720 + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, PLX4720, Cediranib (AZD-2171) and Koselugo (selumetinib) worked synergistically to inhibit cell growth in PLX4720-resistant melanoma cell lines harboring BRAF V600E in culture (PMID: 26461489). 26461489
BRAF V600E thyroid gland 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 glioblastoma sensitive BI2536 + PLX4720 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of BI 2536 and PLX4720 resulted in suppression of downstream signaling, increased apoptotic activity, inhibition of cell proliferation, and tumor growth suppression in glioblastoma cell line xenograft models harboring BRAF V600E (PMID: 26573800). 26573800
BRAF V600E cholangiocarcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, combination treatment with Tafinlar (dabrafenib) and Mekinist (trametinib) in a patient with metastatic cholangiocarcinoma harboring BRAF V600E who progressed on chemotherapy led to a sustained metabolic response for six months (PMID: 33537843). 33537843
BRAF V600E low grade glioma sensitive 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 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 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 colorectal cancer predicted - sensitive JSI-1187 Preclinical - Cell line xenograft Actionable In a preclinical study, JSI-1187 treatment in a colorectal cancer cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor regression and dose-dependent tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). detail...
BRAF V600E glioblastoma sensitive 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 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 melanoma predicted - sensitive 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 colorectal cancer sensitive Cetuximab + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, Koselugo (selumetinib) and Erbitux (cetuximab) combination treatment inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E basal cell carcinoma predicted - sensitive 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 melanoma predicted - sensitive JSI-1187 Preclinical - Cell line xenograft Actionable In a preclinical study, JSI-1187 treatment in a melanoma cell line harboring BRAF V600E led to inhibition of cell proliferation in culture, and tumor growth inhibition in a cell line xenograft model (Cancer Res 2020;80(16 Suppl):Abstract nr 4188). detail...
BRAF V600E 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 colorectal cancer sensitive Pimasertib + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma sensitive Cobimetinib + Vemurafenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (coBRIM) that supported FDA approval, treatment with the combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) resulted in an improved progression-free survival of 12.3 months, compared to 7.2 months with Zelboraf (vemurafenib) plus placebo, among patients with BRAF V600-mutated metastatic melanoma, and BRAF V600E and BRAF V600K are on the companion diagnostic (PMID: 27480103; NCT01689519). 27480103 detail... detail...
BRAF V600E melanoma sensitive 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 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 Guidelines). detail...
BRAF V600E thyroid gland anaplastic carcinoma sensitive Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for patients with advanced or metastatic thyroid gland anaplastic carcinoma harboring BRAF V600E (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
BRAF V600E thyroid gland anaplastic carcinoma sensitive 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 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 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 rectum cancer resistant Panitumumab Guideline Actionable Vectibix (panitumumab), as a monotherapy, is not indicated for use in rectum cancer patients with BRAF V600E (NCCN.org). detail...
BRAF V600E melanoma sensitive SCH772984 Preclinical Actionable In a preclinical study, SCH772984 inhibited growth of melanoma cell lines harboring BRAF V600E in culture (PMID: 26267534). 26267534
BRAF V600E colon cancer sensitive PD-0325901 Preclinical - Cell line xenograft Actionable In a preclinical study, PD-0325901 demonstrated antitumor activity against BRAF V600E colon cancer cell line xenografts (PMID: 16273091). 16273091
BRAF V600E thyroid gland papillary carcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case study, a papillary thyroid carcinoma patient who progressed on Lenvima (lenvatinib) was found to harbor BRAF V600E and was treated with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) on a clinical trial, resulting in partial response in the thyroid bed, cervical and intrathoracic lymph nodes, and pulmonary lesions, with a decrease in target lesion size of 67%, and the patient remained on treatment for 18 months before stopping due to progression (PMID: 31085763). 31085763
BRAF V600E 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 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 salivary gland carcinoma predicted - sensitive Dabrafenib + Trametinib Case Reports/Case Series Actionable In a clinical case report, combined Tafinlar (dabrafenib) and Mekinist (trametinib) treatment of a patient with salivary duct carcinoma harboring BRAF V600E resulted in a reduction of metastatic lesions and stable disease lasting 13 months followed by disease progression (PMID: 30323086). 30323086
BRAF V600E 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 ovarian cancer sensitive 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 high grade glioma predicted - sensitive 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 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 lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in patients harboring BRAF V600E (n=5) mutations, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
BRAF V600E colorectal cancer sensitive 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 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 pancreatic acinar cell adenocarcinoma predicted - sensitive 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 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 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 ganglioglioma sensitive 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 pilocytic astrocytoma sensitive 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 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 Advanced Solid Tumor sensitive Vemurafenib Phase II Actionable In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response of 46% (12/26, 2 complete response, 10 partial response) in patients with advanced solid tumors harboring BRAF V600E, but only 4% (1/23, 1 partial response) in patients harboring non-V600 BRAF mutations (PMID: 29320312; NCT02091141). 29320312
BRAF V600E Advanced Solid Tumor sensitive Vemurafenib Phase II Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 33% (56/172) in patients with advanced solid tumors harboring BRAF V600E, including 5 patients with a complete response and 51 patients with a partial response, and led a duration of response of 13.1 months, a progression-free survival of 5.8 months, and an overall survival of 17.6 months (PMID: 32029534; NCT01524978). 32029534
BRAF V600E Advanced Solid Tumor sensitive Dabrafenib + Trametinib FDA approved Actionable In 3 Phase II trials (ROAR, NCI-MATCH, X2101) that supported FDA approval, Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy demonstrated safety and efficacy in adult and pediatric (6 years or older) patients with advanced solid tumors harboring BRAF V600E (PMID: 34838156, PMID: 32818466, J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002, J Clin Oncol 38, no. 15_suppl (May 20, 2020) 10506; NCT02034110, NCT02465060, NCT02124772). 32818466 detail... detail... 34838156 detail... detail...
BRAF V600E Advanced Solid Tumor sensitive Dabrafenib + Trametinib Phase II Actionable In a Phase II trial (NCI-MATCH), Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy resulted in an objective response rate of 33.3% (11/33) in patients with advanced solid tumors other than melanoma, thyroid, colorectal, and lung cancer harboring BRAF V600E, with a median duration of response of 12 months, median progression-free survival of 9.4 months, and median overall survival not reached (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 3002; NCT02465060). detail...
BRAF V600E melanoma sensitive ASTX029 Preclinical - Cell line xenograft Actionable In a preclinical study, ASTX029 treatment reduced Erk and Rsk phosphorylation, induced cell-cycle arrest, and inhibited growth of a melanoma cell line harboring BRAF V600E in culture and inhibited tumor growth in cell line xenograft models, and was also effective against cells with acquired resistance to Zelboraf (vemurafenib) or Koselugo (selumetinib) (PMID: 34330842). 34330842
BRAF V600E high grade glioma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), responses were seen in glioma patients harboring BRAF V600E (n=24) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 5 patients with a partial response (PMID: 32029534; NCT01524978). 32029534
BRAF V600E high grade glioma predicted - sensitive Vemurafenib Phase II Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 25% (6/24, 1 complete response, 5 partial responses) in patients with gliomas harboring BRAF V600E, with a median progression free survival of 5.5-months, a median overall survival of 28.2 months (PMID: 30351999; NCT01524978). 30351999
BRAF V600E colon cancer sensitive Navitoclax + Trametinib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human colon cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E thyroid gland cancer sensitive Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) inhibited growth of both parental thyroid cancer cell lines harboring BRAF V600E and those acquired Sprycel (dasatinib)-resistance in culture (PMID: 27222538). 27222538
BRAF V600E colon 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 colorectal cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, colorectal cancer cell lines harboring a BRAF V600E mutation were sensitive to Nexavar (sorafenib) in culture (PMID: 24885690). 24885690
BRAF V600E intrahepatic cholangiocarcinoma predicted - sensitive Trametinib Case Reports/Case Series Actionable In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment resulted in an objective response rate of 37.9% (11/29) in patients with advanced solid tumors harboring BRAF V600E, of 4 patients with intrahepatic cholangiocarcinoma, 3 achieved a partial response, with individual progression-free survival of 12.8, 9.1, and 29.4 months (PMID: 32758030; NCT02465060). 32758030
BRAF V600E glioblastoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in a partial response 1 week after treatment in a patient with epithelioid type glioblastoma harboring BRAF V600E, although the patient soon passed due to complications (PMID: 31386052). 31386052
BRAF V600E glioblastoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, Zelboraf (vemurafenib) treatment resulted in tumor regression as confirmed by MRI after 3-weeks of treatment in a patient with epithelioid glioblastoma harboring BRAF V600E (PMID: 31217909). 31217909
BRAF V600E glioblastoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in stable disease as best response in 3 of 6 patients with glioblastoma harboring BRAF V600E, with stable disease lasting 3.6, 3.7, and 12.9 months, respectively (PMID: 30351999; NCT01524978). 30351999
BRAF V600E uveal melanoma no benefit YM-254890 Preclinical - Cell culture Actionable In a preclinical study, transformed mouse melanocytes expressing BRAF V600E were insensitive to treatment with YM-254890 (PMID: 33229459). 33229459
BRAF V600E colorectal cancer sensitive Alpelisib + Cetuximab + Encorafenib Preclinical - Cell culture Actionable In a preclinical study, combination therapy consisting of Erbitux (cetuximab), Encorafenib (LGX818) and Alpelisib (BYL719) inhibited survival of colorectal cancer cell lines harboring BRAF V600E in culture (PMID: 27312529). 27312529
BRAF V600E melanoma sensitive BI-69A11 Preclinical Actionable In a preclinical study, BI-69A11 inhibited proliferation and Akt/mTOR signaling in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897, PMID: 20531415). 20531415 26603897
BRAF V600E melanoma sensitive E6201 Case Reports/Case Series Actionable In a Phase I trial, a patient with metastatic melanoma and brain metastasis harboring BRAF V600E demonstrated an ongoing near complete response with an overall survival of more than 8 years, and preclinical analysis of melanoma cell lines harboring homozygous or heterozygous BRAF V600E in culture were sensitive to treatment with E6201 (PMID: 30264293). 30264293
BRAF V600E melanoma sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited Mapk pathway activation and proliferation of melanoma cell lines harboring BRAF V600E mutation in culture (PMID: 24448821). 24448821
BRAF V600E colon adenocarcinoma not applicable N/A Phase III Emerging In a post-hoc analysis of a Phase III trial, BRAF V600E mutations in colon adenocarcinoma patients with microsatellite stable tumors were associated with a shorter disease-free survival and overall survival compared to those patients with microsatellite instability tumors, suggesting that BRAF V600E may serve as a future prognostic biomarker in this patient population (PMID: 26768652). 26768652
BRAF V600E melanoma sensitive 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 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 anaplastic oligodendroglioma sensitive Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). detail...
BRAF V600E melanoma decreased response 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 BI-847325 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with BI-847325 resulted in decreased expression of Mcl-1 and Mek, and inhibited growth of melanoma cell lines harboring BRAF V600E in culture, and inhibited tumor growth in xenograft models of BRAF V600E-positive melanoma, including models with BRAF-inhibitor resistance (PMID: 25873592). 25873592
BRAF V600E melanoma sensitive Dabrafenib + Trametinib Phase II Actionable In a Phase II trial, BRAF V600E positive melanoma patients who progressed on treatment with BRAF inhibitors or the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) were treated again with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) after 12 weeks off treatment, which resulted in a partial response in 35% (8/25) and stable disease in 40% (10/25) (PMID: 28268064). 28268064
BRAF V600E melanoma sensitive Dabrafenib + Trametinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (COMBI-v) that supported FDA approval, the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) resulted in an improved overall survival rate at 12 months (72% vs 65%, HR=0.69, p=0.005), median progression-free survival (11.4 vs 7.3 months, HR=0.56, p<0.001), and objective response rate (64% vs 51%, p<0.001) compared to Zelboraf (vemurafenib) in melanoma patients harboring BRAF V600E or V600K (PMID: 25399551; NCT01597908). detail... detail... 25399551
BRAF V600E melanoma sensitive Dabrafenib + Trametinib Preclinical Actionable In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cells harboring BRAF V600E in culture (PMID: 22389471). 22389471
BRAF V600E 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 pilocytic astrocytoma predicted - sensitive Dabrafenib Case Reports/Case Series Actionable In a clinical case study, Tafinlar (dabrafenib) treatment resulted in a near complete response and resolution of leptomeningeal dissemination in a patient with pilocytic astrocytoma harboring BRAF V600E (PMID: 28784858). 28784858
BRAF V600E melanoma sensitive 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 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 high grade glioma predicted - sensitive PLX4720 + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) and PLX4720 synergistically inhibited growth and induced apoptosis in glioma cell lines in culture, resulted in prolonged survival in cell line xenograft models (PMID: 27217440). 27217440
BRAF V600E pancreatic ductal adenocarcinoma predicted - sensitive 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 ovarian serous carcinoma predicted - sensitive 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 melanoma sensitive DEL-22379 Preclinical - Cell line xenograft Actionable In a preclinical study, DEL-22379 inhibited growth of melanoma cells harboring BRAF V600E with high levels of ERK dimerization in culture and inhibited tumor progression in melanoma xenograft models harboring BRAF V600E (PMID: 26267534). 26267534
BRAF V600E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 inhibited proliferation of melanoma cell lines harboring either monomeric BRAF V600E or dimeric isoform of V600E which conferred Zelboraf (vemurafenib)-resistance in culture (PMID: 27523909). 27523909
BRAF V600E melanoma sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 treatment inhibited Erk phosphorylation and reduced proliferation of a melanoma cells harboring either monomeric BRAF V600E or dimeric isoform (p61) of V600E in culture (PMID: 30559419). 30559419
BRAF V600E melanoma predicted - sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of tumor growth in a melanoma cell line xenograft model harboring BRAF V600E (PMID: 33953400). 33953400
BRAF V600E melanoma 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 colorectal cancer sensitive Bevacizumab + Capecitabine + Vemurafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Zelboraf (vemurafenib) treatment when combined with Xeloda (capecitabine) and Avastin (bevacizumab) enhanced tumor growth inhibition and increased survival in a cell line xenograft model of colorectal cancer harboring BRAF V600E (PMID: 22180495). 22180495
BRAF V600E neuroendocrine tumor predicted - sensitive 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 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 colorectal cancer sensitive Lapatinib + Panobinostat Preclinical Actionable In a preclinical study, Tykerb (lapatinib) and Faridak (panobinostat) worked synergistically to inhibit growth of BRAF V600E mutant colorectal cancer cells in culture (PMID: 21464044). 21464044
BRAF V600E high grade glioma predicted - sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, Belvarafenib (HM95573) treatment led to inhibition of cell viability in a patient-derived glioma cell line harboring BRAF V600E in culture (PMID: 34433654). 34433654
BRAF V600E 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 skin melanoma sensitive Dabrafenib + Trametinib Guideline Actionable Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy is included in guidelines for cutaneous melanoma patients harboring a BRAF V600 activating mutation, such as BRAF V600E, as adjuvant therapy for stage III disease and as systemic therapy for patients with unresectable or metastatic disease (NCCN.org). detail...
BRAF V600E anaplastic oligodendroglioma sensitive Dabrafenib + Trametinib Guideline Actionable Combination of Mekinist (trametinib) and Tafinlar (dabrafenib) is included in guidelines for patients with recurrent anaplastic gliomas harboring BRAF V600E, including anaplastic oligodendroglioma (NCCN.org). detail...
BRAF V600E 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 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 lung non-small cell carcinoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E 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 melanoma sensitive SBI-755199 Preclinical Actionable In a preclinical study, SBI-755199 induced cell death in human melanoma cell lines harboring BRAF V600E in culture (PMID: 26603897). 26603897
BRAF V600E colorectal cancer sensitive 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 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 colorectal cancer sensitive Trametinib Preclinical Actionable In a preclinical study, colorectal cancer cells harboring a BRAF V600E mutation had increased sensitivity to Mekinist (trametinib) compared to other colorectal cancer lines in culture (PMID: 25309914). 25309914
BRAF V600E colorectal cancer sensitive Ulixertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Ulixertinib (BVD-523) inhibited Erk signaling in colorectal cancer cells harboring BRAF V600E, resulted in cell cycle arrest in culture and tumor growth inhibition in cell line xenograft models (PMID: 28939558). 28939558
BRAF V600E melanoma sensitive Navitoclax + Trametinib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Mekinist (trametinib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E melanoma sensitive Navitoclax + Vemurafenib Preclinical Actionable In a preclinical study, Navitoclax (ABT-263) enhanced the inhibitory effect of Zelboraf (vemurafenib) on human melanoma cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E colorectal cancer sensitive 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 thyroid gland papillary carcinoma sensitive 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 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 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 colorectal cancer sensitive Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of colorectal cancer cells harboring BRAF V600E in culture (PMID: 23629727). 23629727
BRAF V600E melanoma no benefit 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 anaplastic astrocytoma sensitive 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 low grade glioma sensitive Cobimetinib + Vemurafenib Guideline Actionable Combination of Zelboraf (vemurafenib) and Cotellic (cobimetinib) is included in guidelines for patients with recurrent or progressive low grade glioma harboring BRAF V600E (NCCN.org). detail...
BRAF V600E lung non-small cell carcinoma sensitive Trametinib + TW-37 Preclinical Actionable In a preclinical study, TW-37 enhanced the inhibitory effect of Mekinist (trametinib) on human non-small cell lung cancer cells harboring BRAF V600E in culture (PMID: 25665005). 25665005
BRAF V600E Erdheim-Chester disease sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is included in guidelines as preferred first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring BRAF V600E (NCCN Guidelines). detail...
BRAF V600E colorectal cancer sensitive Encorafenib Phase I Actionable In a Phase I trial, Encorafenib (LGX818) showed activity in patients with advanced metastatic colorectal cancer harboring a BRAF V600E mutation, resulting in a median progression-free survival of 4 months and a best response of stable disease in 66.7% (12/18) (Ann Oncol (2014) 25 (suppl 4): iv182-iv183). detail...
BRAF V600E 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 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 glioblastoma predicted - sensitive PLX8394 Case Reports/Case Series Actionable In a clinical case study, PLX8349 treatment resulted in a radiographic partial response and complete resolution of symptoms for 7 months in a patient with glioblastoma harboring BRAF V600E, CDKN2A/B loss and CHEK2 T367fs were also identified in the tumor (PMID: 32923904; NCT02428712). 32923904
BRAF V600E skin melanoma sensitive Binimetinib + Encorafenib Guideline Actionable Braftovi (encorafenib) in combination with Mektovi (binimetinib) is included in guidelines as first-line and second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring BRAF V600E or V600K mutations (PMID: 30959471; NCCN.org). detail... 30959471
BRAF V600E high grade glioma sensitive 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 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 melanoma sensitive PLX7904 Preclinical - Cell culture Actionable In a preclinical study, PLX7904 inhibited survival of melanoma cell lines harboring monomeric BRAF V600E as well as cells harboring the Zelboraf (vemurafenib)-resistant dimeric BRAF V600E in culture (PMID: 26466569). 26466569
BRAF V600E rectum cancer sensitive Encorafenib + Panitumumab Guideline Actionable Braftovi (encorafenib) in combination with Vectibix (panitumumab) is included in guidelines as primary or subsequent therapy for patients with rectal cancer harboring BRAF V600E (NCCN.org). detail...
BRAF V600E colorectal cancer predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a Phase I trial, Belvarafenib (HM95573) treatment in a colorectal cancer patient harboring BRAF V600E led to a tumor reduction of 39% after 8 weeks of treatment and a confirmed partial response at 12 weeks, and response to treatment was maintained for 8 weeks (PMID: 33953400; NCT03118817). 33953400
BRAF V600E melanoma sensitive Dabrafenib + Regorafenib + Trametinib Preclinical - Pdx & cell culture Actionable In a preclinical study, combination treatment with Stivarga (regorafenib), Tafinlar (dabrafenib), and Mekinist (trametinib) in a melanoma cell line harboring BRAF V600E resulted in suppression of colony formation in culture, and suppressed tumor growth in patient-derived xenograft (PDX) models (PMID: 33568355). 33568355
BRAF V600E colon cancer sensitive GDC0879 Preclinical - Cell line xenograft Actionable In a preclinical study, GDC0879 inhibited survival of colon cancer cell lines harboring BRAF V600E in cell culture and cell line xenograft models (PMID: 19276360). 19276360
BRAF V600E 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 skin melanoma sensitive 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 skin melanoma no benefit 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 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 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 colorectal cancer sensitive 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 lung non-small cell carcinoma sensitive 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 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 thyroid gland follicular carcinoma sensitive Dabrafenib Guideline Actionable Tafinlar (dabrafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid follicular carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). detail...
BRAF V600E thyroid gland Hurthle cell carcinoma sensitive Vemurafenib Guideline Actionable Zelboraf (vemurafenib) is included in guidelines for patients with recurrent, advanced, or metastatic thyroid Hurthle cell carcinoma harboring BRAF V600E for whom clinical trials are not available or appropriate (NCCN.org). detail...
BRAF V600E melanoma sensitive 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 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 large cell carcinoma predicted - sensitive 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 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 high grade glioma