Application of XIAP antisense to cancer and other proliferative disorders: development of AEG35156/ GEM640.

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Lacasse EC, Kandimalla ER, Winocour P, Sullivan T, Agrawal S, Gillard JW, Durkin J

Application of XIAP antisense to cancer and other proliferative disorders: development of AEG35156/ GEM640.

Ann N Y Acad Sci. 2005 Nov;1058:215-34.

PubMed ID

16394139 [ View in PubMed

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Abstract

Targeting apoptosis control provides a novel therapeutic approach to the treatment of cancer and other proliferative disorders. We summarize the evidence for apoptosis deregulation in cancer and describe the pivotal role of XIAP, the X-linked Inhibitor-of-APoptosis. XIAP is the predominant inhibitor of caspases 3, 7 and 9 in cells, which suppresses the programmed cell death effector capability of these proteases. Evidence is presented validating XIAP as a cancer target. The inhibition or downregulation of XIAP in cancer cells lowers the apoptotic threshold, thereby inducing cell death and/or enhancing the cytotoxic action of chemotherapeutic agents. We describe the development of AEG35156 (also named GEM640), a second generation antisense compound targeting XIAP, from concept to in vivo preclinical proof-of-principle studies, through formal toxicology, and to a phase 1 clinical trial in cancer patients.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
AEG35156	E3 ubiquitin-protein ligase XIAP	Protein	Humans	Unknown	Not Available	Details