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Genetic Subgrouping of Melanoma Reveals New Opportunities for Targeted Therapy

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

Requests for reprints: Keiran S.M. Smalley, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-745-8725; Fax: 813-745-4384; E-mail: keiran.smalley{at}moffitt.org.

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

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]