The role of CD95 system in chemotherapy.

Chemotherapy of malignant tumors, including acute leukemias, is largely based on empirical data and clinical experience. In recent years, it has become clear that anticancer drugs induce apoptosis in target cells. Activation of the CD95 system initiated by induction of CD95 ligand/receptor interaction has been shown to contribute to drug-induced apoptosis in certain systems. However, some groups also have shown that drug-induced apoptosis occurs independently of CD95 triggering. Drug-induced activation of apoptotic pathways appears to include parallel or sequential activation of death receptor systems and, most importantly, changes in mitochondrial function with concomitant release of apoptogenic factors. Activation of downstream caspases, such as caspase 3 or caspase 9, seems to be the most critical mediator of a drug-induced cell death. The identification of the crucial elements of drug-induced apoptosis and activation of effector caspases will certainly provide new insights into the molecular determinants of chemosensitivity or chemoresistance of malignant tumors and leukemias. Copyright 1999 Harcourt Publishers Ltd.