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| Gene | BRAF |
| Variant | mutant |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | BRAF mutant indicates an unspecified mutation in the BRAF gene. |
| Associated Drug Resistance | |
| Category Variants Paths |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 TP53 wild-type | melanoma | sensitive | KRT-232 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KRT-232 (AMG 232) inhibited growth of a melanoma cell line with wild-type TP53, that also harbored a BRAF mutation, in culture and inhibited tumor growth in a TP53 wild-type BRAF-mutant melanoma cell line xenograft model (PMID: 25567130). | 25567130 |
| BRAF mut TP53 wild-type | colorectal cancer | sensitive | CGM097 + Dabrafenib + Navitoclax + PF-04217903 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), CGM097, Tafinlar (dabrafenib), and PF04217903 resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and wild-type TP53 in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
| BRAF mut TP53 wild-type | Advanced Solid Tumor | predicted - sensitive | 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 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 | 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 | 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 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, SAR260301 inhibited proliferation of PTEN deficient melanoma cells harboring BRAF mutations in culture and suppressed tumor growth in cell line xenograft models (PMID: 27196754). | 27196754 |
| BRAF mut PTEN loss | melanoma | sensitive | 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 | 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 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 | 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 | 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 | GSK2636771 + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, GSK2636771 and NVP-AEW541 combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | AZD6482 + 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 | 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 + Encorafenib | Preclinical | Actionable | In a preclinical study, AZD6482 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN wild-type | melanoma | no benefit | Encorafenib + GSK2636771 | Preclinical | Actionable | In a preclinical study, GSK2636771 and Encorafenib (LGX818) combination treatment did not enhance growth inhibition compared to single agent in PTEN wild-type melanoma cell lines harboring BRAF mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 | Preclinical | Actionable | In a preclincal study, AZD6482 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | TGX-221 | Preclinical | Actionable | In a preclincal study, TGX-221 inhibited Akt activation and proliferation in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | 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 | decreased response | Alpelisib | Preclinical | Actionable | In a preclincal study, melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations were less sensitive to Alpelisib (BYL719)-induced growth inhibition in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | Alpelisib + AZD6482 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | Alpelisib + AZD6482 + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | 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 | 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 | AZD6482 + Binimetinib + NVP-AEW541 | Preclinical | Actionable | In a preclinical study, combination treatment consists of AZD6482, Binimetinib (MEK162), and NVP-AEW541 efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | AZD6482 + 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 + Binimetinib + Encorafenib | Preclinical | Actionable | In a preclinical study, combination treatment consisting of AZD6482, Binimetinib (MEK162), Encorafenib (LGX818), and Alpelisib (BYL719) efficiently induced apoptosis in melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations in culture (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | 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 | GSK2636771 + unspecified IGF-1R antibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination treatment consisting of GSK2636771 and a figitumumab-like antibody inhibited tumor growth in xenograft models of melanoma cell lines harboring BRAF mutations and PTEN inactivating mutations (PMID: 26577700). | 26577700 |
| BRAF mut PTEN inact mut | melanoma | sensitive | 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 | 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 RB1 loss | melanoma | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line harboring a BRAF mutation and loss of RB1 demonstrated a decreased response to Ibrance (palbociclib) treatment in culture when compared to treatment of melanoma cell lines wild-type for BRAF (PMID: 27488531). | 27488531 |
| BRAF mut RB1 loss | melanoma | decreased response | 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 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, a melanoma cell line with a BRAF mutation and loss of RB1 demonstrated minimal sensitivity when treated with the combination of Ibrance (palbociclib) and Mekinist (trametinib) in culture (PMID: 27488531). | 27488531 |
| BRAF mut TP53 mut | colorectal cancer | sensitive | Alpelisib + Dabrafenib + Erlotinib + Navitoclax | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
| BRAF mut PIK3CA wild-type | colorectal cancer | predicted - sensitive | 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 |