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Gene | BRAF |
Variant | class 2 |
Impact List | unknown |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF Class 2 variants are BRAF variants that activate BRAF and downstream signaling in a dimer-dependent, RAS-independent manner (PMID: 28783719, PMID: 26343582). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF class 2 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF class 2 | pancreatic cancer | predicted - sensitive | Exarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Exarafenib (KIN-2787) treatment led to inhibition of tumor growth in a pancreatic cell line xenograft model harboring a BRAF class 2 mutation (J of Clin Oncol 39, no. 15_suppl (May 20, 2021) 3116-3116). | detail... |
BRAF class 2 | colorectal cancer | decreased response | Cetuximab | Clinical Study | Actionable | In a clinical study, colorectal cancer patients harboring class 2 BRAF mutations demonstrated a decreased response to treatment with the combination of either Erbitux (cetuximab) or Vectibix (panitumumab) plus chemotherapy compared to those with class 3 BRAF mutations, with a response rate of 8% (1/12) vs 50% (14/28) (P=0.02), respectively, in first, second, third or later-line setting and a response rate of 17% (1/6) vs 78% (7/9) (P=0.04), respectively, in the first or second-line setting (PMID: 31515458). | 31515458 |
BRAF class 2 | colorectal cancer | decreased response | Panitumumab | Clinical Study | Actionable | In a clinical study, colorectal cancer patients harboring class 2 BRAF mutations demonstrated a decreased response to treatment with the combination of either Erbitux (cetuximab) or Vectibix (panitumumab) plus chemotherapy compared to those with class 3 BRAF mutations, with a response rate of 8% (1/12) vs 50% (14/28) (P=0.02), respectively, in first, second, third or later-line setting and a response rate of 17% (1/6) vs 78% (7/9) (P=0.04), respectively, in the first or second-line setting (PMID: 31515458). | 31515458 |
BRAF class 2 | Advanced Solid Tumor | predicted - sensitive | BDTX-4933 | Preclinical - Cell culture | Actionable | In a preclinical study, BDTX-4933 inhibited proliferation of cells expressing a BRAF class 2 mutation in culture (Eur J Cancer (2022), Vol 174, Supplement 1: S86). | detail... |
BRAF class 2 | Advanced Solid Tumor | predicted - sensitive | Exarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Exarafenib (KIN-2787) was tolerated and resulted in a partial response in 17.6% (6/34) and stable disease in 23.5% (8/34) of patients with BRAF-driven advanced solid tumors or NRAS-driven melanoma, including a partial response in 1 patient harboring a BRAF class 2 mutation (Cancer Res (2023) 83 (8_Supplement): CT032; NCT04913285). | detail... |
BRAF class 2 | Advanced Solid Tumor | predicted - sensitive | DCC-3084 | Preclinical - Cell culture | Actionable | In a preclinical study, DCC-3084 inhibited downstream signaling and proliferation in cells expressing a BRAF class 2 mutation in culture (Cancer Res (2023) 83 (7_Supplement): 4045). | detail... |