vemurafenib

Overview

Selective BRAF V600E inhibitor.

Evidence in the corpus

  • Eight histiocytosis patients with BRAF V600E identified through Make-an-IMPACT were treated with vemurafenib or dabrafenib; matched targeted therapy yielded clinical benefit in 17/18 treated histiocytosis patients (mean duration 21.7 months, range 6–40+) PMID:36862133.
  • Vemurafenib (BRAF inhibitor) was among MAPK-pathway directed therapies evaluated in a tumor-agnostic BRAF fusion cohort (N=241, 52 histologies); combination BRAF+MEK inhibition was less durable than MEK monotherapy; 15 patients acquired BRAF fusions as resistance to prior EGFR TKIs (including vemurafenib context) PMID:38922339.
  • BRAF mutations (predominantly V600E) identified in melanoma WGS study provide basis for vemurafenib sensitivity in BRAF-mutant cutaneous melanoma PMID:22622578
  • BRAF V600 mutations present in 60% of melanoma discovery cohort (n=121); vemurafenib cited as established RAF inhibitor predicting response in BRAF V600-mutant melanoma PMID:22817889
  • BRAF V600E mutations confirmed as most frequent driver (~50%) in cutaneous melanomas (Yale, n=147); vemurafenib cited alongside dabrafenib as BRAF-targeted therapies with known clinical benefit PMID:22842228
  • BRAF V600E occurs in 1.7% (5/291) of primary GBM and is never co-occurring with NF1 alteration; the TCGA GBM 2013 analysis cites BRAF V600E as a rationale for vemurafenib-class therapy in a small molecularly selected GBM subset PMID:24120142.
  • WES of 45 BRAF V600 melanoma patients treated with vemurafenib or dabrafenib (DeCOG cohort) identified resistance alterations in 23/45 patients (51%), including MAP2K1/MAP2K2 mutations and MITF amplification conferring cross-resistance to RAF/MEK inhibition PMID:24265153
  • Referenced as an acquired-resistance paradigm (BRAF-mutant melanoma + vemurafenib) to motivate combination regimens and second-generation inhibitors for HCC targeted therapy PMID:24735922
  • BRAF V600E mutations occur in 3% of pancreatic ductal adenocarcinomas (mutually exclusive with KRAS); patient-derived cell line PDA_014 (BRAF V600E) was as sensitive to vemurafenib (PLX-4032) as MNT1 melanoma control cells across ERK phosphorylation, cell-cycle, and viability assays PMID:25855536
  • Vemurafenib is one of three FDA-approved BRAF-targeted therapies (with dabrafenib and trametinib) for the BRAF-mutant subtype of melanoma (52% of 318 TCGA cases; V600E/K/R mutations); BRAF non-hot-spot mutations and fusions (ATG7-BRAF, TAX1BP1-BRAF) also identified in TCGA melanoma cohort PMID:26091043
  • Referenced as prior MAPKi context in Hugo et al. anti-PD-1 melanoma study (n=38): 14/38 patients had prior MAPK-inhibitor therapy including vemurafenib, dabrafenib, or trametinib; MAPKi-induced transcriptional programs overlap substantially with the IPRES innate anti-PD-1 resistance signature, raising concern that prior/concurrent vemurafenib therapy may compromise subsequent anti-PD-1 response in BRAF-mutant melanoma PMID:26997480

Resistance mechanisms

  • Not reported in corpus.

Cancer types (linked)

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22622578

This page was processed by crosslinker on 2026-05-14. - PMID:22817889

This page was processed by crosslinker on 2026-05-14. - PMID:22842228

This page was processed by crosslinker on 2026-05-14. - PMID:24120142

This page was processed by crosslinker on 2026-05-14. - PMID:24265153

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26997480

This page was processed by entity-page-writer on 2026-05-15.