Targeting the IAP family of caspase inhibitors as an emerging therapeutic strategy.
The IAPs (inhibitor of apoptosis proteins) are a family of caspase inhibitors that block the execution phase of apoptosis. Overexpression of IAPs confers chemoresistance and, in some groups of patients, is associated with a poor prognosis. Given their role in the development and progression of solid tumors and hematologic malignancies, efforts are underway to develop therapeutic IAP inhibitors, with a focus on X-linked IAP (XIAP) and survivin. Antisense oligonucleotides that target XIAP and survivin have been developed and are currently in phase I clinical trial. Small-molecules that bind and inhibit XIAP have also been identified and are in the process of clinical development. This review focuses on the preclinical data that support the development of IAP-targeted therapies.
Schimmer
Aaron D
AD
Princess Margaret Hospital, University of Toronto, Toronto Ontario M5G 2M9, Canada. aaron.schimmer@utoronto.ca
Dalili
Shadi
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000627:therapeutic use
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein