title: Advances in targeted therapy for melanoma.
abstract: Metastatic melanoma remains an aggressive malignancy conferring a very poor prognosis, and standard chemotherapeutic and immunologic treatments have not demonstrated an overall survival benefit. No molecularly targeted therapy is approved for the treatment of advanced melanoma. Melanoma is a molecularly heterogeneous malignancy, and optimal treatment in a given patient is likely to depend on the presence of specific molecular abnormalities. Aberrations in components of signal transduction pathways have been identified that modulate melanoma proliferation and survival. Mutations that activate the mitogen activated protein kinase (MAPK) pathway via BRAF or NRAS are present in the majority of melanomas arising on skin intermittently exposed to the sun. Mutations that activate the KIT oncogene are more commonly present in melanomas arising from mucosal, acral, or chronic sun-damaged sites. Inhibitors of the MAPK pathway and of KIT are currently undergoing clinical investigation. In this article, we review advances in targeted strategies to treat different subgroups of patients with melanoma.
authors.affiliation: Instructor of Medicine, Department of Medical Oncology at Dana Farber Cancer Institute in Boston, Massachusetts 02115, USA. pfriedlander@partners.org
authors.forename: Philip
authors.initials: P
authors.lastname: Friedlander
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D019009:Proto-Oncogene Proteins c-kit