Drug-resistance in human melanoma

Advanced malignant melanoma has a poor prognosis since chemotherapy is most ly ineffective due in part to the intrinsic and/or extrinsic resistance of melanoma cells to systemic treatment with anti-neoplastic agents. The reaso ns for the chemoresistant phenotype are unknown. The relevance of well-anal yzed drug-resistance mechanisms, e.g., intracellular/ extracellular transpo rt and induction of certain enzyme systems, is reviewed. Most anti-cancer d rugs kill susceptible cells through induction of apoptosis. Therefore, it a ppears that differences in the apoptotic pathways which lead to apoptotic d eficiency may account for the ability of some tumor cells to resist drug th erapy. Human melanomas, which are characteristically drug-resistant, are mo re likely to have altered apoptotic pathways and fewer pro-apoptotic molecu les. Tumor cells with these characteristics are seldom sensitive to drugs. The complexity of the molecular variants involved in signal transduction al ong apoptotic pathways suggests that the cell may have a variety of possibi lities for regulating apoptosis and generating apoptotic deficiency. Thus, apoptosis and apoptotic deficiency should be analyzed to better clarify the mechanisms of melanoma resistance. (C) 2001 Wiley-Liss, Inc.