title: Targeting IAP proteins for therapeutic intervention in cancer.
abstract: Evasion of apoptosis is one of the crucial acquired capabilities used by cancer cells to fend off anticancer therapies. Inhibitor of apoptosis (IAP) proteins exert a range of biological activities that promote cancer cell survival and proliferation. X chromosome-linked IAP is a direct inhibitor of caspases - pro-apoptotic executioner proteases - whereas cellular IAP proteins block the assembly of pro-apoptotic protein signalling complexes and mediate the expression of anti-apoptotic molecules. Furthermore, mutations, amplifications and chromosomal translocations of IAP genes are associated with various malignancies. Among the therapeutic strategies that have been designed to target IAP proteins, the most widely used approach is based on mimicking the IAP-binding motif of second mitochondria-derived activator of caspase (SMAC), which functions as an endogenous IAP antagonist. Alternative strategies include transcriptional repression and the use of antisense oligonucleotides. This Review provides an update on IAP protein biology as well as current and future perspectives on targeting IAP proteins for therapeutic intervention in human malignancies.
authors.affiliation: Institute for Experimental Cancer Research in Pediatrics, Goethe University Frankfurt, Komturstr. 3a, 60528 Frankfurt, Germany. simone.fulda@kgu.de
authors.forename: Simone
authors.initials: S
authors.lastname: Fulda
authors.forename: Domagoj
authors.initials: D
authors.lastname: Vucic
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D051636:X-Linked Inhibitor of Apoptosis Protein