sorafenib

Overview

Sorafenib is an oral multi-kinase inhibitor with FDA approvals in hepatocellular carcinoma, differentiated thyroid carcinoma, and renal cell carcinoma. In osteosarcoma it is an NCCN-listed option for relapsed/refractory disease.

Evidence in the corpus

  • KDR (VEGFR2) kinase domain mutations identified in LUAD (n=188, 4 kinase-domain variants, rare amplifications) suggest potential benefit from VEGFR inhibitors such as sorafenib in KDR-mutant tumours. PMID:18948947
  • In the UCLA PDTO sarcoma screen, sorafenib was one of the recurrent NCCN-listed top-five regimens identified for osteosarcoma samples, appearing as part of the actionable backbone for this histology alongside regorafenib, etoposide, cisplatin, doxorubicin, cabozantinib, gemcitabine, docetaxel, and everolimus. PMID:39305899
  • PDTOs from patients with rapidly progressing tumors at follow-up showed increased sensitivity to sorafenib (p=0.042) compared to non-rapidly-progressing specimens. PMID:39305899
  • Activating RET mutations in metastatic MTCs (PN3, PN7, PN8) and high PIK3R2 expression (PN1) informed sorafenib recommendations in the POG NEN WGTA cohort (n=28) PMID:24326773
  • VEGFA focal gain at 6p21 is reported as a predictor of sorafenib benefit in HCC; no targeted therapy has exceeded sorafenib in phase III HCC trials as of early 2014, framed as the central translational gap PMID:24735922
  • First-line HCC standard of care (SHARP trial): sorafenib vs placebo median OS 10.7 vs 7.9 months (HR 0.69, 95% CI 0.55–0.87, P<0.001); standard for Child–Pugh A, BCLC-C/post-TACE-B from 2007 through 2017; no predictive biomarkers identified; STORM adjuvant trial was negative PMID:24798001
  • Nominated for Triple-WT melanoma subtype (14% of 318 TCGA cases) to target co-amplified PDGFRA/KDR at 4q12 alongside imatinib, crenolanib, regorafenib, and pazopanib; Triple-WT lacks hot-spot BRAF/RAS/NF1 mutations PMID:26091043
  • Multi-kinase inhibitor; proposed as therapeutic candidate for BRAF D594-mutant GCT (3 BRAF mutations including D594N, D594G in 180 advanced GCT patients) per Appendix Table A2 PMID:27646943
  • Identified as sorafenib-sensitive agent for ARAF S214Y/S214P hotspot mutations (2 patients) in 860-patient MSK-IMPACT LUAD cohort based on prior preclinical work; these rare ARAF hotspots cited as potentially actionable PMID:28336552.

Resistance mechanisms

  • Not reported in corpus.

Cancer types (linked)

Sources

  • PMID:18948947 — Ding et al. 2008, Nature. Exome-scale somatic mutation landscape of 188 LUAD tumours; KDR kinase domain mutations implicate VEGFR inhibitors including sorafenib.
  • PMID:39305899 — Duminuco et al. 2024, UCLA PDTO sarcoma functional screen; NCCN-listed osteosarcoma regimen; progressive-disease phenotype association.

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This page was processed by crosslinker on 2026-05-14. - PMID:24798001

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

This page was processed by crosslinker on 2026-05-14. - PMID:27646943

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