Molecular profiling of melanoma and the evolution of patient-specific therapy.

It recently has become clear that multiple molecular subtypes of melanoma likely exist that may be associated with clinical response to defined therapeutic modalities. Gene expression profiling has revealed a signature that is associated with clinical benefit to melanoma vaccines, with preliminary work suggesting a correlation with response to other immunotherapy agents as well. Activating mutations in B-Raf and c-kit are associated with clinical response to the specific kinase inhibitors PLX4032 and imatinib, respectively. Several other signal transduction pathways have been found to be constitutively active or mutated in other subsets of melanoma tumors that are potentially targetable with new agents. Together, these emerging data suggest the evolution of a new paradigm in melanoma therapy in which molecular analysis of the tumor will be used to assign the most appropriate therapeutic modality for each individual patient, to maximize therapeutic success.