ArticleCancer discovery2014
Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy.
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 565 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
565 citing papers in PubMed, 983 citations in OpenAlex.
- Exploratory Analysis of Biomarkers and Treatment Outcomes from the COLUMBUS Study in BRAF V600E/K-Mutant Advanced or Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial.Nature communications · 2026Trial
- Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.Cell reports. Medicine · 2021Trial
- Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Cancer metastasis: biological mechanisms, therapeutic bottlenecks, and emerging interventions.Journal of hematology & oncology · 2026Review
- Recent Developments and Structure-Activity Relationships of BRAF Inhibitors for Cancer Drug Discovery.Archiv der Pharmazie · 2026Review
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- New Treatment Strategy and Future Research Direction for BRAF-Mutated Cancer.Cancer science · 2026Review
- Targetable alterations and personalized treatment in ameloblastoma: results from a prospective observational precision oncology study.NPJ precision oncology · 2026Article
- FGFR1 but not S6K1/2 drives intrinsic BRAF inhibitor resistance in melanoma.Cell death discovery · 2026Article
- Targeting Melanoma-Associated Fibroblasts to Overcome Cancer Stem Cell-Driven Drug Resistance.Journal of the American College of Surgeons · 2026Article
- Targeting Activated Pathways in Doxorubicin-Resistant TNBC Alters Signaling, Survival and EMT: A Double-Edged Sword.International journal of molecular sciences · 2026Article
- Article
- CRISPR screens reveal YAP/TEAD axis as a mediator of drug-tolerant cells in EGFR-mutant NSCLC.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Marked response to dabrafenib plus trametinib in a patient with BRAF V600E-mutant pancreatic hepatoid carcinoma: a case report and systematic analysis of 57 cases.Frontiers in oncology · 2026Article
- DNV-TC: a developmental network vulnerability-based classification system for precision oncology.Frontiers in cell and developmental biology · 2026Article
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- The safety and efficacy of encorafenib plus binimetinib for brain metastases: a systematic review and meta-analysis.Discover oncology · 2025Review
- Fragment-based discovery enables direct targeting of the melanoma oncogene MITF.Nature communications · 2025Article
- Genomic copy-number variants drive apoptotic evasion underlying acquired resistance to immune checkpoint inhibitors.Immunity · 2025Article
505 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAF(V600)-mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that mitogen-activated protein kinase reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification, and alternative splicing being most common. We also detected PI3K-PTEN-AKT-upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions in both core drug escape pathways were commonly detected concurrently in the same tumor or among multiple tumors from the same patient. Beyond harboring extensively heterogeneous resistance mechanisms, melanoma regrowth emerging from BRAF inhibitor selection displayed branched evolution marked by altered mutational spectra/signatures and increased fitness. Thus, melanoma genomic heterogeneity contributes significantly to BRAF inhibitor treatment failure, implying upfront, cotargeting of two core pathways as an essential strategy for durable responses.
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What OpenQuestion holds
Registered trials
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.