CHEMORESISTANCE OF HUMAN-MALIGNANT MELANOMA - CELLULAR AND MOLECULAR ASPECTS

Cutaneous malignant melanoma (MM) is to date solely curable by a compl ete 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 resist ance of MM to systemic treatment with antineoplastic drugs. The reason s for the intrinsic chemoresistance phenotype are to date widely unkno wn and a matter of beginning exploration. Several drug resistance mech anisms have been identified or, the level of drug delivery to the tumo r 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 w ith chemotherapy failure in vivo suggest an involvement of cellular re sistance factors. Beside the classical multidrug resistance (MDR) mech anisms such as the overexpression of drug-transporting molecules and d etoxifying enzymes the general sensitivity of a cell with respect to r espond to a damage with programmed cell death (PCD) gains increasing i mportance in the study of cellular drug resistance. Data currently ava ilable and future perspectives on the possible role of these different protective mechanisms in the chemoresistance of MM are briefly discus sed.