Inhibitor of apoptosis proteins: fascinating biology leads to attractive tumor therapeutic targets

Cell death inhibition is a very successful strategy that cancer cells employ to combat the immune system and various anticancer therapies. Inhibitor of apoptosis (IAP) proteins possess a wide range of biological activities that promote cancer survival and proliferation. One of them, X-chromosome-linked IAP is a direct inhibitor of proapoptotic executioners, caspases. Cellular IAP proteins regulate expression of antiapoptotic molecules and prevent assembly of proapoptotic protein signaling complexes, while survivin regulates cell division. In addition, amplifications, mutations and chromosomal translocations of IAP genes are associated with various malignancies. Several therapeutic strategies have been designed to target IAP proteins, including a small-molecule approach that is based on mimicking the IAP-binding motif of an endogenous IAP antagonist - the second mitochondrial activator of caspases. Other strategies involve antisense nucleotides and transcriptional repression. The main focus of this article is to provide an update on IAP protein biology and perspectives on the development of IAP-targeting therapeutics.