ArticleNature2017
Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 344 papers, 5 of them syntheses that pooled it.
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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.
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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
344 citing papers in PubMed, 5 syntheses or guidelines pooled it, 553 citations in OpenAlex.
- Mindfulness-based interventions for gambling disorder: A systematic review.Journal of behavioral addictions · 2026Pooled it
- How to find a needle in a haystack: a systematic review on targeting KRAS wild-type pancreatic cancer.Future oncology (London, England) · 2024Pooled it
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.JCO precision oncology · 2022Pooled it
- Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).Genetics in medicine : official journal of the American College of Medical Genetics · 2022Guideline
- 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
- AKT mutant allele-specific activation dictates pharmacologic sensitivities.Nature communications · 2022Trial
- Practical management of BRAF inhibitors in glioma: toxicity and resistance.CNS oncology · 2026Review
- Article
- High-resolution measurement of ERK activation state reveals determinants of BRAF regulation and drug sensitivity.bioRxiv : the preprint server for biology · 2026Article
- Unveiling BRAF Mutations in Non-small Cell Lung Cancer: State of the Art and Future Perspectives.Lung · 2026Review
- SMARCA4-deficient Anaplastic Thyroid Carcinoma: A Hitherto Unreported Case.Virchows Archiv : an international journal of pathology · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- ERK1/2 Inhibitor Ulixertinib in Pan-cancer Patients with BRAF Fusions or Non-V600E/K Mutations: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1L.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- Recent Developments and Structure-Activity Relationships of BRAF Inhibitors for Cancer Drug Discovery.Archiv der Pharmazie · 2026Review
- Evolving patterns of co-mutations from tumor initiation to metastatic progression.Nature genetics · 2026Article
- CDK9 inhibition sensitizes intrinsically resistantActa pharmaceutica Sinica. B · 2026Article
- Contemporary design of small-molecule kinase modulators: orthosteric, allosteric and induced-proximity strategies.Nature reviews. Drug discovery · 2026Review
- Global patterns of mutational profiles in biliary tract cancer.Journal of hepatology · 2026Article
284 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Approximately 200 BRAF mutant alleles have been identified in human tumours. Activating BRAF mutants cause feedback inhibition of GTP-bound RAS, are RAS-independent and signal either as active monomers (class 1) or constitutively active dimers (class 2). Here we characterize a third class of BRAF mutants-those that have impaired kinase activity or are kinase-dead. These mutants are sensitive to ERK-mediated feedback and their activation of signalling is RAS-dependent. The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling. The model suggests that dysregulation of signalling by these mutants in tumours requires coexistent mechanisms for maintaining RAS activation despite ERK-dependent feedback. Consistent with this hypothesis, melanomas with these class 3 BRAF mutations also harbour RAS mutations or NF1 deletions. By contrast, in lung and colorectal cancers with class 3 BRAF mutants, RAS is typically activated by receptor tyrosine kinase signalling. These tumours are sensitive to the inhibition of RAS activation by inhibitors of receptor tyrosine kinases. We have thus defined three distinct functional classes of BRAF mutants in human tumours. The mutants activate ERK signalling by different mechanisms that dictate their sensitivity to therapeutic inhibitors of the pathway.
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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.