XIAP as target for therapeutic apoptosis in prostate cancer.
Progression to androgen independence combined with chemotherapy resistance remains one of the primary obstacles to the improvement of quality of life and survival for patients with advanced prostate cancer. One unique feature of the androgen-independent cell population is that they still retain the appropriate machinery for apoptosis. Therefore, identifying a cure for prostate cancer requires identification and reversal of the antiapoptotic mechanisms responsible for drug resistance and/or newer therapies that bypass the apoptosis-resistance pathways. The key element in the apoptotic pathway is the processing and activation of caspases by either a mitochondrial-dependent or -independent cascade of events. XIAP, a member of the inhibitor of apoptosis family of proteins (IAP), has been identified as a potent caspase inhibitor. XIAP expression seems to be regulated by the presence of a rare sequence, internal ribosome entry sequence (IRES) in its 5' untranslated region (5' UTR) which facilitates its antiapoptotic function during any kind of induced-cellular stress like radiation and chemotherapy, making it an attractive therapeutic target. This review attempts to present an overview of the interaction between cell survival and death pathways, mechanism of XIAP action and recent studies supporting XIAP as an emerging therapeutic target.
Devi
Gayathri R
GR
Cancer and Endocrine Program, AVI BioPharma, Inc, Corvallis, Oregon 97333, USA. grdevi@avibio.com
D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000502:physiology; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein
D000728:Androgens; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human