No longer a molecular black box--new clues to apoptosis and drug resistance in melanoma.

Disseminated melanoma is a radiation- and chemotherapy-refractory neoplasm for which no standard therapy currently exists. So far, genetic and molecular studies have revealed few non-random chromosomal abnormalities and infrequent mutational spectra. Consequently, the precise molecular determinants responsible for melanoma progression are yet to be delineated. Recent studies, however, have identified defects at multiple levels of the apoptosis program in melanoma, which provided new clues to drug resistance of this highly aggressive neoplasm. The process of apoptosis provides a conceptual framework to link melanoma genetics with the outcome of melanoma therapy. Hence, the genes and proteins that control apoptosis provide exciting new targets for rationally designed anti-melanoma therapeutic strategies.