Mutation-driven drug development in melanoma - PubMed (original) (raw)

Review

Mutation-driven drug development in melanoma

Keith T Flaherty et al. Curr Opin Oncol. 2010 May.

Abstract

Purpose of review: The identification of mutations in signal transduction pathways that are central in melanoma pathophysiology has provided new therapeutic targets for drug development. The purpose of this review is to define those oncogenes for which there are preclinical data supporting clinical trials and to summarize results from clinical investigations.

Recent findings: CKIT mutations were first reported in 2005 but are present in only a small subpopulation of melanoma patients. The validation of inhibitors developed in gastrointestinal stromal tumors has taken several years, but recent evidence suggests that responses can be seen in CKIT mutant melanoma. First reported in 2002, BRAF is mutated in 50% of all melanomas and subsets of other cancers. The melanoma field is leading the clinical trials evaluating the value of targeting BRAF and MEK in BRAF mutant tumors. Results from the first clinical trial with a potent and selective BRAF inhibitor clearly show the therapeutic promise of this approach.

Summary: Larger clinical trials are needed to fully define the efficacy of BRAF and CKIT-directed therapy in melanoma, but early results suggest that this strategy will transform treatment options. Additional potential targets have been identified, and clinical trials evaluating novel drugs against them are underway.

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Figure 1

Mutation & deletion in MAP kinase, PI3 kinase & p16 pathways in melanoma

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