Abstract
BRAF V600E is an emerging drug target in lung cancer, but the clinical significance of non-V600 BRAF mutations in lung cancer and other malignancies is less clear. Here, we report the case of a patient with metastatic lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. We calculated a structure model of this very rare type of mutated BRAF kinase to explain the molecular mechanism of drug resistance. This information may help to develop effective targeted therapies for cancers with non-V600 BRAF mutations.
Keywords:
BRAF; Biomarker; Dabrafenib; Lung cancer; Melanoma; Targeted therapy; Vemurafenib.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
MeSH terms
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Adenocarcinoma / diagnosis
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / genetics*
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Adenocarcinoma of Lung
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Aged
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / therapeutic use*
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Codon
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DNA Mutational Analysis
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Drug Resistance, Neoplasm / genetics*
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Humans
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Indoles / chemistry
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Indoles / therapeutic use*
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Lung Neoplasms / diagnosis
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics*
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Male
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Models, Molecular
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Molecular Conformation
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Mutation*
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Positron-Emission Tomography
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Proto-Oncogene Proteins B-raf / chemistry
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Proto-Oncogene Proteins B-raf / genetics*
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Sulfonamides / chemistry
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Sulfonamides / therapeutic use*
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Tomography, X-Ray Computed
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Vemurafenib
Substances
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Antineoplastic Agents
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Codon
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Indoles
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Sulfonamides
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Vemurafenib
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Proto-Oncogene Proteins B-raf