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Profile Name | BRAF V600K |
Gene Variant Detail | |
Relevant Treatment Approaches | BRAF Inhibitor MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor RAF Inhibitor (Pan) |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 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 | predicted - sensitive | GSK2126458 | Preclinical - Cell culture | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K with NRAS Q61K 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 | 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 | 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 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 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 | 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 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 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 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 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 del exon4-10 BRAF V600K | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a BRAF exon 4-10 deletion (reported as p55) variant was identified in the post-progression plasma ctRNA of a patient with metastatic melanoma harboring BRAF V600K who previously responded to treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33216826). | 33216826 |