ArticleOncotarget2017
Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.JCO precision oncology · 2022Pooled it
- BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy.NPJ precision oncology · 2025Article
- Article
- Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision.Science advances · 2024Article
- Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.International journal of molecular sciences · 2024Review
- Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.Drugs in R&D · 2024Review
- An updated literature on BRAF inhibitors (2018-2023).Molecular diversity · 2024Review
- Clinical Response of Advanced Lung Adenocarcinoma with Class III BRAF G466V Missense Mutation to Dabrafenib and Trametinib: A Case Report.OncoTargets and therapy · 2024Article
- Clinicopathological Features of Non-Small Cell Lung Carcinoma with BRAF Mutation.Current oncology (Toronto, Ont.) · 2023Article
- Unique Spectrum of Activating BRAF Alterations in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- Non-small-cell lung cancer: how to manageDrugs in context · 2023Review
- Molecular Pathways and Mechanisms of BRAF in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- Molecular matched targeted therapies for primary brain tumors-a single center retrospective analysis.Journal of neuro-oncology · 2022Article
- Recognition of BRAF by CDC37 and Re-Evaluation of the Activation Mechanism for the Class 2 BRAF-L597R Mutant.Biomolecules · 2022Article
- DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition.Cancer discovery · 2022Article
- [Current Advance in Targeted Treatment and Immunotherapy for BRAF-mutant Advanced Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma.Haematologica · 2021Article
- Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately half of BRAF-mutated Non-small cell lung cancers (NSCLCs) harbor a non-V600 BRAF mutation, accounting for ∼40,000 annual deaths worldwide. Recent studies have revealed the benefits of combined targeted therapy with a RAF-inhibitor (Dabrafenib) and a MEK-inhibitor (Trametinib) in treating V600 BRAF mutant cancers, including NSCLC. In contrast, sensitivity of non-V600 BRAF mutations to these inhibitors is not documented. Non-V600 mutations can either increase or impair BRAF kinase activity. However, impaired BRAF kinases can still activate the ERK pathway in a CRAF-dependent manner. Herein, beyond describing a cohort of BRAF mutant NSCLC patients and functionally analyzing 13 tumor-derived BRAF mutations, we demonstrate that both types of non-V600 BRAF mutations can be sensitive to clinically relevant doses of Dabrafenib and Trametinib in HEK293T cells, in lung epithelial cellular model (BEAS-2B) and in human cancer cell lines harboring non-V600 BRAF mutations. ERK activity induced by both types of these mutations is further reduced by combinatorial drug treatment. Moreover, the combination leads to more prolonged ERK inhibition and has anti-proliferative and pro-apoptotic effects in cells harboring both types of non-V600 BRAF mutations. This study provides a basis for the clinical exploration of non-V600 BRAF mutant lung cancers upon treatment with Trametinib and Dabrafenib.
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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.