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BRAF

Also known as B-Raf

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Tumour types

colorectal cancer, melanoma, non-small cell lung cancer

BRAF encodes a serine/threonine kinase downstream of RAS in the MAPK pathway.

V600E is the predominant activating variant; other class II/III BRAF alterations exist but generally have lower sensitivity to BRAF inhibitors.

Clinical significance

  • BRAF V600E/V600K-mutant melanoma is eligible for BRAF plus MEK inhibitor combination therapy.

    fda — FDA-approved product labeling for BRAF/MEK inhibitor combinations

  • In BRAF V600E-mutant metastatic colorectal cancer, BRAF inhibitor combinations are used following progression on prior therapy, typically combined with anti-EGFR therapy.

    pmc — PMC Open Access Subset, oncology literature

FDA-approved treatments

  • Tafinlar (dabrafenib) — BRAF V600E/V600K-mutant unresectable or metastatic melanoma, in combination with trametinib (Mekinist); BRAF V600E-mutant metastatic NSCLC, in combination with trametinib [fda]
  • Braftovi (encorafenib) — BRAF V600E/V600K-mutant unresectable or metastatic melanoma, in combination with binimetinib (Mektovi); BRAF V600E-mutant metastatic colorectal cancer, in combination with cetuximab [fda]
  • Zelboraf (vemurafenib) — BRAF V600E-mutant unresectable or metastatic melanoma [fda]

Prevalence

BRAF V600E mutations occur in approximately 50% of cutaneous melanomas, 8%-15% of colorectal cancers, and 1%-3% of NSCLC. [fda]

Tests / detection method

PCR-based mutation assays, NGS

Therapeutic pipeline

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