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Profile Name | BRAF G596R |
Gene Variant Detail | |
Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
BRAF G596R | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) reduced Erk signaling and inhibited proliferation of a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28783719). | 28783719 |
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 | colorectal cancer | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased proliferation and increased apoptosis, and enhanced ERK inhibition compared to either agent alone in a colorectal cancer cell line harboring BRAF G596R in culture (PMID: 28947956). | 28947956 |
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 | 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 | 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 | 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 |