Molecular genetics and targeted therapies for cutaneous melanoma

Therapy for advanced melanoma remains inadequate and novel approaches are needed. The network of signal transduction abnormalities in melanoma is being elucidated with the help of the discovery of somatic genetic mutations. Preclinical evidence supports targeting the pathways that are upregulated as a consequence of activation of oncogenes or loss of tumor suppressor genes. The best-studied pathways include the MAP kinase pathway and PI3 kinase pathway. The activity of these pathways appears to account for some of the resistance to chemotherapy that is well-noted clinically in this disease. Therefore, inhibitors of these pathways may offer rational agents to combine with conventional chemotherapy. More preclinical research is needed to understand how to combine signal transduction inhibitors in a way that will obviate the need for chemotherapy.