ABSTRACT
Cancer cells have evolved diff erent molecular mechanisms to promote their proliferation and survival. One of the major strategies that cancer cells employ to ensure their survival is inhibition of cell death triggered by the immune system and various anti-cancer therapies. Th e family of inhibitors of apoptosis (IAP) proteins unites structurally related molecules that possess a broad spectrum of activities required for inhibition of cell death and promotion of survival signaling pathways. Th ese anti-apoptotic properties are best exemplifi ed in X-chromosomelinked IAP and its ability to inhibit caspases, executioner proteases of apoptosis. Other IAP family members have developed alternative survival capabilities, such as regulation of nuclear factor-kappaB (NF-κB) pathways by cellular IAP1 and 2, and regulation of cell division by survivin. Combined with their elevated expression in cancer tissues, it is not surprising that IAP proteins are important contributors to the development of human malignancies. Eff orts to target IAP proteins in tumors have mainly focused on designing small molecules that mimic IAP-binding motif of endogenous IAP antagonist second mitochondrial activator of caspases, SMAC. In addition, several other IAP-targeting strategies, including
antisense oligonucleotides, transcriptional repression, and immunotherapy have also been initiated in the hope of providing therapeutic benefi t to cancer patients.
