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Skin Cancer & Melanoma

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We describe areas where major inroads were initially achieved by targeting angiogenesis and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit–activating mutations in GIST and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec).

A new target of melanoma tumors has been identified that may be promising as part of a novel combination therapy for melanoma. In a study published in Nature Medicine, researchers have identified that more than half of melanoma cases, both early and late-stage, may have higher levels of MDM4, a p53-interacting protein.

The new therapies that became available for advanced melanoma over the past year-the anti-CTLA4 antibody ipilimumab (Yervoy) and the selective BRAF inhibitor vemurafenib (Zelboraf)-represent promising new options for these patients, whose prognosis was heretofore almost universally dismal. However, the advent of new treatment strategies has made treatment decisions more complex.

Melanoma has become the poster cancer for genomic research. The identification of a driver mutation in the BRAF gene found in approximately 40% of metastatic melanoma patients and the subsequent approval last year of the targeted BRAF inhibitor, vemurafenib, has resulted in a surge of both clinical and laboratory research.