X-linked inhibitor of apoptosis protein as a therapeutic target

Dysregulation of apoptosis has been shown to contribute to many diseases, including cancer formation, development and resistance, as well as neurodegenerative and autoimmune disorders. One mechanism through which tumour cells are believed to acquire resistance to apoptosis is by overexpression of X-linked inhibitor of apoptosis protein (XIAP), which belongs to a family of inhibitor of apoptosis proteins. When XIAP is over-expressed, cancer cells are rendered resistant to apoptosis, both intrinsically and in response to chemotherapy and radiotherapy. Significant progress has been made in targeting XIAP therapeutically, both directly and indirectly through the modulation of other molecules involved in the apoptotic pathway. This review introduces XIAP from its molecular origins, discusses its modulation and potential as a novel drug target, and considers future therapeutic perspectives.