Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Gene | BRAF |
Variant | act mut |
Impact List | unknown |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF act mut indicates that this variant results in a gain of function in the Braf protein. However, the specific amino acid change has not been identified. |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 | 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 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 | Advanced Solid Tumor | sensitive | PLX8394 | Preclinical | Actionable | In a preclinical study, PLX8394 had been shown to block survival and growth of vemurafenib/PLX4720-resistant cells harboring distinct BRAF activating mutations (PMID: 24422853). | 24422853 |
BRAF act mut | colorectal cancer | 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 | colorectal cancer | no benefit | Venetoclax + VX-11e | Preclinical - Cell culture | Actionable | In a preclinical study, inhibition of Erk signaling by VX-11e did not sensitize colorectal cancer cell lines harboring KRAS or BRAF activating mutations to Venclexta (venetoclax) in culture (PMID: 27974663). | 27974663 |
BRAF act mut | lung non-small cell carcinoma | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | CC-91516 | Preclinical - Patient cell culture | Actionable | In a preclinical study, CC-91516 treatment induced apoptosis and inhibited viability of cancer cells harboring BRAF activating mutations, and inhibited ex vivo colony formation from patient-derived xenograft (PDX) models in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). | detail... |
BRAF act mut | colorectal cancer | predicted - sensitive | CC-91516 | Preclinical - Biochemical | Actionable | In a preclinical study, CC-91516 inhibited Mapk signaling in BRAF-mutant colorectal cancer cells (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). | detail... |
BRAF act mut | melanoma | predicted - sensitive | Ipilimumab + Nivolumab | Clinical Study | Actionable | In a systematic review, an analysis of several clinical trials demonstrated Opdivo (nivolumab) plus Yervoy (ipilimumab) resulted in improved overall survival (OS) compared to BRAF plus MEK inhibitor in BRAF-mutant advanced melanoma patients when considering the entire study period, and analysis of the period beginning 12 months after treatment initiation demonstrated significantly greater OS and progression-free survival (PMID: 33556898; NCT01844505, NCT01584648, NCT01597908, NCT01909453, NCT01689519). | 33556898 |
BRAF act mut | colorectal cancer | sensitive | BCA101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, treatment with BCA101 resulted in a tumor growth inhibition of 31% compared to 8% with Erbitux (cetuximab) in a BRAF-mutant colorectal cancer cell line and human peripheral blood mononuclear cells coimplantation xenograft model (PMID: 37074042). | 37074042 |