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Targeting the apoptosis pathway in prostate cancer
Robert R Zielinski1, Bernhard J Eigl, Kim N Chi
1BC Cancer Agency, Vancouver, British Columbia, Canada V5Z 4E6.
Cancer Journal (Sudbury, Mass.)
|January 23, 2013
Summary
New agents targeting apoptosis pathways show promise for treating metastatic prostate cancer. These therapies aim to restore programmed cell death, potentially overcoming treatment resistance in advanced disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Metastatic prostate cancer treatment has advanced, yet novel therapeutic targets are crucial.
- Apoptosis (programmed cell death) dysregulation is linked to treatment resistance and progression in castration-resistant prostate cancer.
- Restoring apoptotic responses presents a promising therapeutic strategy.
Purpose of the Study:
- To review agents in clinical development targeting apoptosis via intrinsic and extrinsic pathways for prostate cancer.
- To highlight therapeutic strategies aimed at overcoming treatment resistance.
- To discuss the potential of novel apoptosis-targeting agents in combination therapies.
Main Methods:
- Review of clinical development status for agents targeting Bcl2 checkpoints.
- Examination of humanized antibodies to death receptors.
- Analysis of agents targeting inhibitors of apoptosis proteins (IAPs).
- Assessment of small mitochondria-derived activator of caspases (SMAC) mimetics.
- Evaluation of antisense therapies targeting cytoprotective chaperones.
Main Results:
- Single-agent activity has been observed for several apoptosis-targeting agents.
- Agents targeting apoptosis pathways are being developed for combination therapies with standard treatments.
- OGX-011 (custirsen), targeting clusterin, is in Phase III trials for castration-resistant prostate cancer.
Conclusions:
- Agents targeting apoptosis pathways offer a novel approach for metastatic prostate cancer.
- Combination therapy with standard treatments is the likely clinical development path.
- Further research and clinical trials are needed to establish the efficacy of these agents.
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