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Biochem Pharmacol. 2011 Aug 1;82(3):201-9. doi: 10.1016/j.bcp.2011.05.015. Epub 2011 May 25.

Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma.

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1
Program in Molecular Oncology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.

Abstract

The discovery of activating BRAF V600E mutations in 50% of all cutaneous melanomas has revolutionized the understanding of melanoma biology and provided new strategies for the therapeutic management of this deadly disease. Highly potent small molecule inhibitors of BRAF are now showing great promise as a novel therapeutic strategy for melanomas harboring activating BRAF V600E mutations and are associated with high levels of response. This commentary article discusses the latest data on the role of mutated BRAF in the development and progression of melanoma as the basis for understanding the mechanism of action of BRAF inhibitors in the preclinical and clinical settings. We further address the issue of BRAF inhibitor resistance and outline the latest insights into the mechanisms of therapeutic escape as well as describing approaches to prevent and abrogate the onset of both intrinsic and acquired drug resistance. It is likely that our evolving understanding of melanoma genetics and signaling will allow for the further personalization of melanoma therapy with the goal of improving clinical responses.

PMID:
21635872
PMCID:
PMC4001781
DOI:
10.1016/j.bcp.2011.05.015
[Indexed for MEDLINE]
Free PMC Article

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