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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Management of prostate cancer. Part 1: chemoprevention
1Department of Urology, Royal Surrey County Hospital, Guildford, GU2 7XX, UK. sooriakumaran@gmail.com
Abstract:
Numerous agents have been investigated in prostate cancer prevention. Many manipulate sex steroid levels or function, some regulate response to oxidative stress and others affect tumor proliferation and/or apoptosis. Some are postulated to even affect downstream targets, such as cyclooxygenase-2, which has been shown to be elevated in prostate cancer by most investigators. The evidence for all these potential chemopreventive agents is critically reviewed. While the current information base is vast, level 1 evidence is lacking, and ongoing trials are not due to provide such evidence for many years to come. In addition, the current lack of ability to accurately differentiate clinically important prostate cancer from latent disease makes chemoprevention in this setting even more challenging. Currently, no reliable biomarkers that can act as surrogate endpoints for the development of clinically relevant prostate cancer exist, which makes performing large chemoprevention trials expensive. At present, there is little to suggest that the urologist or General Practitioner should be recommending any particular chemopreventive agent to either the general population or those deemed to be at higher risk of contracting prostate cancer.
Insights
Current prostate cancer chemoprevention lacks level 1 evidence. Reliable biomarkers are needed to guide effective prevention strategies and identify clinically significant disease, making recommendations challenging.
Area of Science:
- Oncology
- Preventive Medicine
- Urology
Background:
- Numerous agents targeting sex steroids, oxidative stress, proliferation, apoptosis, and cyclooxygenase-2 have been explored for prostate cancer prevention.
- Existing research on prostate cancer chemoprevention is extensive but lacks robust, high-level evidence.
Purpose of the Study:
- To critically review the evidence supporting various agents for prostate cancer chemoprevention.
- To assess the current challenges and limitations in developing effective prostate cancer prevention strategies.
Main Methods:
- Comprehensive literature review of existing studies on prostate cancer chemopreventive agents.
- Analysis of the evidence base, considering mechanisms of action and downstream targets like cyclooxygenase-2.
Main Results:
- A significant lack of level 1 evidence exists for current prostate cancer chemopreventive agents.
- Ongoing trials will not yield definitive evidence for several years.
- Difficulty in distinguishing clinically significant prostate cancer from latent disease complicates prevention efforts.
Conclusions:
- No reliable biomarkers currently exist to serve as surrogate endpoints for clinically relevant prostate cancer, increasing trial costs.
- Urologists and general practitioners have insufficient evidence to recommend specific chemopreventive agents for the general population or high-risk individuals.
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