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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.
PMID: 16304383 [PubMed - in process]
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Cited by 4 PubMed Central articles
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Impact of XIAP protein levels on the survival of myeloma cells.
Desplanques G, Giuliani N, Delsignore R, Rizzoli V, Bataille R, Barillé-Nion S.
Haematologica. 2009 Jan; 94(1):87-93. Epub 2008 Nov 10.
[Haematologica. 2009]
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Small-molecule XIAP antagonist restores caspase-9 mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells.
Cillessen SA, Reed JC, Welsh K, Pinilla C, Houghten R, Hooijberg E, Deurhof J, Castricum KC, Kortman P, Hess CJ, et al.
Blood. 2008 Jan 1; 111(1):369-75. Epub 2007 Oct 4.
[Blood. 2008]
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The X-linked inhibitor of apoptosis protein (XIAP) is up-regulated in metastatic melanoma, and XIAP cleavage by Phenoxodiol is associated with Carboplatin sensitization.
Kluger HM, McCarthy MM, Alvero AB, Sznol M, Ariyan S, Camp RL, Rimm DL, Mor G.
J Transl Med. 2007 Jan 26; 5:6. Epub 2007 Jan 26.
[J Transl Med. 2007]
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