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B-RAF Inhibitors: An Evolving Role in the Therapy of Malignant Melanoma

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Abstract

Immunotherapy and chemotherapy benefit few patients with metastatic melanoma, and even fewer experience durable survival benefit. These poor results come from treating melanoma as a single homogeneous disease. Recently, it has been shown that targeting activated tyrosine kinases (oncogenes) can mediate striking clinical benefits in several cancers. In 2002, a mutation at the V600E amino acid of the BRAF serine/threonine kinase was described as present in over 50% of melanomas. The mutation appeared to confer a dependency by the melanoma cancer cell on its activation of the MAP kinase pathway. The frequency and specificity of this mutation (95% at V600E of BRAF) suggests that it may be a potential target for therapy, and recent results with one inhibitor, PLX4032/RG7204, bare this out. This review updates the status of BRAF inhibitors in melanoma and what may be on the horizon.

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Disclosure

Dr. Sosman is a consultant for and has received honorarium from Roche.

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Authors and Affiliations

  1. Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA

    Cynthia Shepherd, Igor Puzanov & Jeffrey A. Sosman

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  1. Cynthia Shepherd
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  2. Igor Puzanov
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Correspondence to Cynthia Shepherd.

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Shepherd, C., Puzanov, I. & Sosman, J.A. B-RAF Inhibitors: An Evolving Role in the Therapy of Malignant Melanoma. Curr Oncol Rep 12, 146–152 (2010). https://doi.org/10.1007/s11912-010-0095-2

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