Genetic Subgrouping of Melanoma Reveals New Opportunities for Targeted Therapy

¹Molecular Oncology Program and Department of Cutaneous Oncology, The Moffitt Cancer Center & Research Institute, Tampa, Florida; and Divisions of ²Medical Genetics and ³Hematology-Oncology, Department of Medicine, and ⁴The Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

^* To whom correspondence should be addressed. E-mail: keiran.smalley{at}moffitt.org.

	Abstract

The discovery of activating oncogenic BRAF V600E mutations in the majority of melanomas has not yet been translated into more effective therapy. The failure of agents may be due to lack of sufficiently targeted therapeutics, but is more likely based on the activation of multiple oncogenic pathways in melanomas in addition to the mitogen-activated protein kinase signaling pathway. In contrast, there are groups of melanomas that instead rely on either c-KIT or CRAF signaling that may be amenable to single-agent targeted therapy. In the current review, we discuss how knowledge about these new melanoma subgroups may lead to improved strategies for treating melanomas harboring BRAF V600E mutations. [Cancer Res 2009;69(8):3241–4]

Key Words: melanoma, BRAF, c-KIT, CRAF, targeted therapy