Apoptosis and the response to anticancer therapy

Apoptosis is a distinctive form of cell death that reflects cleavage of a s ubset of intracellular polypeptides by proteases known as caspases. Two maj or intracellular caspase cascades, one activated predominately by death rec eptor ligands and the other triggered by various cellular stresses, includi ng DNA damage and microtubule disruption, have been delineated. Activation of these protease cascades is tightly regulated by a number of polypeptides , including Bcl-2 family members, inhibitor of apoptosis proteins, and seve ral protein kinases. The demonstration that many antineoplastic agents indu ce apoptosis in susceptible cells raises the possibility that factors affec ting caspase activation and activity might be important determinants of ant icancer drug sensitivity. Here, we review recent studies describing the reg ulation of apoptotic pathways and identify potential implications of these findings for resistance to antineoplastic agents. Curr Opin Oncol 2001, 13: 453-462 (C) 2001 Lippincott Williams & Wilkins, Inc.