dabrafenib

Overview

Selective BRAF V600E/K kinase inhibitor.

Evidence in the corpus

  • Used (with vemurafenib) in 8 histiocytosis patients with BRAF V600E identified through the Make-an-IMPACT direct-to-patient profiling program; matched RAF/MEK therapy yielded clinical benefit in 17/18 histiocytosis patients (mean duration 21.7 months) PMID:36862133.
  • Dabrafenib (BRAF inhibitor) was among MAPK-pathway directed therapies evaluated in BRAF fusion-positive tumors (N=241, 52 histologies at MSK); combination BRAF+MEK inhibition was less durable (median 1 month) than MEK inhibitor monotherapy (median 8 months) across all treated patients PMID:38922339.
  • BRAF V600-mutant cutaneous melanomas (Yale, n=147); dabrafenib cited alongside vemurafenib as an established BRAF-targeted therapy with clinical benefit in BRAF-mutant melanoma PMID:22842228
  • WES of 45 BRAF V600 melanoma patients treated with vemurafenib or dabrafenib identified MAP2K2 mutations (V35M, L46F, C125S, N126D) conferring >100-fold cross-resistance to dabrafenib and trametinib; MAP2K1 mutants conferred 10–80-fold dabrafenib resistance in A375 cells PMID:24265153
  • In multiple myeloma, dabrafenib paradoxically activated MAPK and promoted growth in BRAF-WT, KRAS/NRAS-mutant cell lines; conversely, dabrafenib + trametinib combined selectively killed BRAF-mutant (K601N) U266 MM cells without benefit in BRAF-WT lines PMID:24434212
  • BRAF V600E-mutant CCA (3–7% iCCA, near 0% eCCA): ROAR basket phase II ORR ~47% in 43 CCA patients, mPFS ~9 mo, mOS ~14 mo in combination with trametinib PMID:25526346
  • One of three FDA-approved BRAF-targeted therapies for the BRAF-mutant subtype of cutaneous melanoma (52% of 318 TCGA cases; V600E n=124, V600K n=18, V600R n=3, K601 n=5); nominated alongside vemurafenib and trametinib in TCGA melanoma integrative analysis 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 with the IPRES innate anti-PD-1 resistance signature, suggesting prior dabrafenib may compromise anti-PD-1 efficacy in BRAF-mutant melanoma PMID:26997480
  • Matched therapy context for BRAF V600E (level 2A) in 860-patient MSK-IMPACT LUAD cohort; 55.6% of BRAF V600E patients received matched therapy (which included BRAF ± MEK inhibitor combinations) with 75% clinical benefit PMID:28336552.

Resistance mechanisms

  • Not reported in corpus.

Cancer types (linked)

Sources

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

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

This page was processed by crosslinker on 2026-05-14. - PMID:24434212

This page was processed by crosslinker on 2026-05-14. - PMID:25526346

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. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14.