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Updated: Aug 24, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
XIAP as target for therapeutic apoptosis in prostate cancer
1Cancer and Endocrine Program, AVI BioPharma, Inc, Corvallis, Oregon 97333, USA. grdevi@avibio.com
Abstract:
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.
Insights
Targeting XIAP (inhibitor of apoptosis protein) may reverse chemotherapy resistance in advanced prostate cancer. Reversing antiapoptotic mechanisms is crucial for improving patient survival and quality of life.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Advanced prostate cancer progression to androgen independence is linked to chemotherapy resistance.
- Androgen-independent cancer cells retain apoptosis machinery, suggesting a targetable pathway.
- Apoptosis resistance mechanisms are key obstacles to improving survival and quality of life.
Purpose of the Study:
- To review the interaction between cell survival and death pathways.
- To elucidate the mechanism of XIAP (inhibitor of apoptosis protein) action.
- To present XIAP as an emerging therapeutic target for prostate cancer.
Main Methods:
- Review of scientific literature on apoptosis, caspases, and XIAP.
- Analysis of XIAP's role in mediating resistance to chemotherapy and radiation.
- Examination of the internal ribosome entry sequence (IRES) in XIAP's 5' untranslated region (5' UTR).
Main Results:
- XIAP is a potent caspase inhibitor, crucial for apoptosis resistance.
- XIAP expression is regulated by an IRES in its 5' UTR, facilitating antiapoptotic function under cellular stress.
- XIAP's role in resistance to radiation and chemotherapy is highlighted.
Conclusions:
- Reversing antiapoptotic mechanisms is essential for treating advanced prostate cancer.
- XIAP is a significant mediator of drug resistance and an attractive therapeutic target.
- Targeting XIAP offers a potential strategy to overcome chemotherapy resistance in prostate cancer.
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