ArticleCancer discovery2014
The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 523 papers, 5 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
523 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.JCO precision oncology · 2025Pooled it
- Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.JCO precision oncology · 2022Pooled it
- Systematic review and meta-analysis of genomic alterations in acral melanoma.Pigment cell & melanoma research · 2022Pooled it
- Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.Journal for immunotherapy of cancer · 2021Pooled it
- The Predictive Value ofFrontiers in immunology · 2021Pooled it
- Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Article
- Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations.Cell reports · 2026Article
- Article
- Understanding and overcoming innate and acquired MAPK inhibition resistance in anaplastic thyroid cancer.Cell reports. Medicine · 2026Article
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Genomic, Clinical, and Spatial Predictors of Durable Response to BRAF/MEK Inhibition inbioRxiv : the preprint server for biology · 2026Article
- PHI-501, a dual inhibitor of RAF and DDR1/2, overcomes MAPK drug resistance in Melanoma.Cancer cell international · 2026Article
- Associations of Tumor Somatic Mutations and Genetic Alterations with Survival Outcomes in Melanoma Patients Treated with Ipilimumab.Journal of clinical medicine · 2026Article
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Malignant Melanoma: Landscape of Molecular Markers.Biomedicines · 2026Article
- BRAF and MEK inhibition beyond dabrafenib-trametinib in advanced thyroid cancer: a real-world case series.Frontiers in endocrinology · 2026Article
- A Systematic Review of Evidence for the Cost of Therapeutic Resistance in Cancer.bioRxiv : the preprint server for biology · 2025Article
- TRMU Confers Resistance of Melanoma Cells to Vemurafenib through Modulating Mitochondrial Activities.Journal of proteome research · 2025Article
- Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma.Biomolecules · 2025Article
463 more citing papers are in PubMed but not listed here.
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33 authors.
Funding
Abstract
Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood. We performed whole-exome sequencing on formalin-fixed, paraffin-embedded tumors from 45 patients with BRAF(V600)-mutant metastatic melanoma who received vemurafenib or dabrafenib monotherapy. Genetic alterations in known or putative RAF inhibitor resistance genes were observed in 23 of 45 patients (51%). Besides previously characterized alterations, we discovered a "long tail" of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance. In three cases, multiple resistance gene alterations were observed within the same tumor biopsy. Overall, RAF inhibitor therapy leads to diverse clinical genetic resistance mechanisms, mostly involving MAPK pathway reactivation. Novel therapeutic combinations may be needed to achieve durable clinical control of BRAF(V600)-mutant melanoma. Integrating clinical genomics with preclinical screens may model subsequent resistance studies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.