Inhibitors of apoptosis: clinical implications in cancer

Abstract

Inhibitor of apoptosis (IAP) family comprises a group of endogenous proteins that function as main regulators of caspase activity and cell death. They are considered the main culprits in evasion of apoptosis, which is a fundamental hallmark of carcinogenesis. Overexpression of IAP proteins has been documented in various solid and hematological malignancies, rendering them resistant to standard chemotherapeutics and radiation therapy and conferring poor prognosis. This observation has urged their exploitation as therapeutic targets in cancer with promising pre-clinical outcomes. This review describes the structural and functional features of IAP proteins to elucidate the mechanism of their anti-apoptotic activity. We also provide an update on patterns of IAP expression in different tumors, their impact on treatment response and prognosis, as well as the emerging investigational drugs targeting them. This aims at shedding the light on the advances in IAP targeting achieved to date, and encourage further development of clinically applicable therapeutic approaches.