Chemoresistance of human malignant melanoma: Cellular and molecular aspects

Cutaneous malignant melanoma (MM) is to date solely curable by a complete surgical removal of the tumor at early stages, whereas no curative treatment modality exists in case of dissemination. This unfavorable prognosis in advanced stages is caused in part by the intrinsic resistance of MM to systemic treatment with antineoplastic drugs. The reasons for the intrinsic chemoresistance phenotype are to date widely unknown and a matter of beginning exploration. Several drug resistance mechanisms have been identified or, the level of drug delivery to the tumor cell as well as on the level of the tumor cell itself. In case of MM, both the high chemoresistance of MM cell lines and its correlation with chemotherapy failure in vivo suggest an involvement of cellular resistance factors. Beside the classical multidrug resistance (MDR) mechanisms such as the overexpression of drug-transporting molecules and detoxifying enzymes the general sensitivity of a cell with respect to respond to a damage with programmed cell death (PCD) gains increasing importance in the study of cellular drug resistance. Data currently available and future perspectives on the possible role of these different protective mechanisms in the chemoresistance of MM are briefly discussed.