BRAF as a Target for Cancer Therapy

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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BRAF as a Target for Cancer Therapy



Anti-Cancer Agents in Medicinal Chemistry, 11(3): 285-295.

Author(s): Rodrigo Dienstmann and Josep Tabernero.

Affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.

Abstract

Tumors with mutations in the gene encoding the serine-threonine protein kinase BRAF are dependent on the MAPK signaling pathway for their growth, what offers an opportunity to test oncogene-targeted therapy. Mutations at the position V600 of BRAF were described in approximately 8% of all solid tumors, including 50% of melanomas, 30 to 70% of papillary thyroid carcinomas and 5 to 8% of colorectal adenocarcinomas. Specific BRAF kinase inhibitors are undergoing rapid clinical development and promising data on efficacy have been demonstrated in activated mutant BRAF V600 melanomas. This review article will address: (a) preclinical data on the antitumor activity of BRAF inhibitors in cell lines/ in vivo models and their opposing functions as inhibitors or activators of the MAPK pathway, depending on the cellular context; (b) drug development from non-selective RAF inhibitors to selective BRAF inhibitors, such as PLX4032 and GSK2118436, with emphasis in the clinical efficacy and toxicity of these agents; and (c) possible mechanisms of resistance to BRAF inhibitors and strategies to overcome its development in BRAF mutant tumors.

Keywords:

BRAF V600, BRAF inhibitor, melanoma, RAF inhibitor, resistance, targeted therapy, ARAF, BRAF, MAPK kinase, C-terminal kinase domain, phosphatase, NRAS mutations, cytotoxic chemotherapy, hospho-ERK, PTEN.



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Article Details

Volume: 11
Issue Number: 3
First Page: 285
Last Page: 295
Page Count: 11
DOI: 10.2174/187152011795347469
Price: $58
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