Abstract
The BRAF inhibitor (BRAFi) vemurafenib improves survival of patients with melanoma with BRAFV600E mutations. However, effects of sustained BRAFis on BRAFi-resistant melanomas with dual mutations in BRAF and NRAS are not well characterized. Jandova and Wondrak (2021) report that vemurafenib selectively enhances expression of genes involved in the epithelial-to-mesenchymal transition in BRAFV600E/NRASQ61K melanoma cells, paradoxically promoting tumor growth and metastasis in mice. This preclinical study provides compelling reasons to be cautious in the use of BRAFis in patients with NRAS-driven melanoma.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Line, Tumor
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Drug Resistance, Neoplasm / genetics
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Friends
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Humans
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Indoles / pharmacology
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Indoles / therapeutic use
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Melanoma* / drug therapy
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Melanoma* / genetics
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Melanoma* / metabolism
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Mice
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Mutation
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf* / genetics
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Proto-Oncogene Proteins B-raf* / metabolism
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use
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Vemurafenib / pharmacology
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Vemurafenib / therapeutic use
Substances
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Indoles
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Protein Kinase Inhibitors
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Sulfonamides
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Vemurafenib
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BRAF protein, human
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Proto-Oncogene Proteins B-raf