ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2020
Molecular Landscape of BRAF-Mutant NSCLC Reveals an Association Between Clonality and Driver Mutations and Identifies Targetable Non-V600 Driver Mutations.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Unveiling BRAF Mutations in Non-small Cell Lung Cancer: State of the Art and Future Perspectives.Lung · 2026Review
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- Computational and pharmacophore-based study of Camellia sinensis phytochemicals targeting BRAF in melanoma.Scientific reports · 2025Article
- Benchmarking large-scale single-cell RNA-seq analysis.bioRxiv : the preprint server for biology · 2025Article
- Harnessing CRISPR/Cas9 to overcome targeted therapy resistance in non‑small cell lung cancer: Advances and challenges (Review).Oncology reports · 2025Review
- Combining Molecular Dynamics and Machine Learning to Predict Drug Resistance Causing Variants of BRAF in Colorectal Cancer.Molecules (Basel, Switzerland) · 2025Article
- Prevalence, genetic variations and clinical outcomes of BRAF-V600 mutated advanced NSCLC in China: a retrospective real-world multi-centre study.EBioMedicine · 2025Article
- Combined BRAF G469A mutation and echinoderm microtubule associated protein like-4-anaplastic lymphoma kinase rearrangement with resistance: A case report and review of literature.World journal of clinical oncology · 2025Article
- Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence.Military Medical Research · 2025Review
- Outcomes with frontline immune checkpoint inhibitors among individuals withFrontiers in oncology · 2025Article
- Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.International journal of molecular sciences · 2024Review
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- Resistance mechanisms of non-small cell lung cancer and improvement of treatment effects through nanotechnology: a narrative review.Journal of thoracic disease · 2024Review
- A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies.Nature cancer · 2024Article
- Molecular characterization of Chinese patients with small bowel adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Efficacy of trametinib in a metastatic urothelial carcinoma patient with a BRAF mutation.IJU case reports · 2024Article
- A large-scale, multicenter characterization of BRAF G469V/A-mutant non-small cell lung cancer.Cancer medicine · 2024Article
- RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- BRAFNPJ precision oncology · 2024Review
- BRAF/MEK-targeted therapy in BRAF ex15 p.T599dup mutation-driven NSCLC: a case report.Journal of cancer research and clinical oncology · 2024Review
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
introductionApproximately 4% of NSCLC harbor BRAF mutations, and approximately 50% of these are non-V600 mutations. Treatment of tumors harboring non-V600 mutations is challenging because of functional heterogeneity and lack of knowledge regarding their clinical significance and response to targeted agents.
methodsWe conducted an integrative analysis of BRAF non-V600 mutations using genomic profiles of BRAF-mutant NSCLC from the Guardant360 database. BRAF mutations were categorized by clonality and class (1 and 2: RAS-independent; 3: RAS-dependent). Cell viability assays were performed in Ba/F3 models. Drug screens were performed in NSCLC cell lines.
resultsA total of 305 unique BRAF mutations were identified. Missense mutations were most common (276, 90%), and 45% were variants of unknown significance. F468S and N581Y were identified as novel activating mutations. Class 1 to 3 mutations had higher clonality than mutations of unknown class (p < 0.01). Three patients were treated with MEK with or without BRAF inhibitors. Patients harboring G469V and D594G mutations did not respond, whereas a patient with the L597R mutation had a durable response. Trametinib with or without dabrafenib, LXH254, and lifirafenib had more potent inhibition of BRAF non-V600-mutant NSCLC cell lines than other MEK, BRAF, and ERK inhibitors, comparable with the inhibition of BRAF V600E cell line.
conclusionsIn BRAF-mutant NSCLC, clonality is higher in known functional mutations and may allow identification of variants of unknown significance that are more likely to be oncogenic drivers. Our data indicate that certain non-V600 mutations are responsive to MEK and BRAF inhibitors. This integration of genomic profiling and drug sensitivity may guide the treatment for BRAF-mutant NSCLC.
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