Bypassing Cancer Resistance by Antagonizing “Inhibitor of Apoptosis Proteins” (IAPs)

Since cell death by apoptosis is critical for the maintenance of tissue homeostasis, dysregulation of the cell's intrinsic death program may promote tumor formation and progression. In addition, most anticancer therapies used in clinical oncology primarily act by triggering apoptosis in cancer cells. Therefore, defects in apoptosis programs, for example aberrant expression of antiapoptotic proteins, may render cancer cells resistant to current treatment approaches. “Inhibitor of Apoptosis Proteins” (IAPs) are expressed at high level in many human cancers and block apoptosis at a central point by binding to and inhibiting effector caspases. Thus, strategies that target IAPs, e.g. antisense approaches or small molecule inhibitors, open new perspectives to either directly trigger apoptosis in cancer cells or to restore sensitivity for apoptosis induction by cytotoxic therapies.