ReviewProstate cancer chemoprevention: Current status and future prospects
Introduction
In recent years, cancer chemoprevention emerged as one of the major approaches for reducing cancer burden. The term ‘chemoprevention’ was first introduced by Michael B Sporn in 1976, referring to the prevention of cancer development by natural forms of vitamin A. This strategy seems to be promising for reducing cancer incidence both in well defined “high-risk” groups and also in the general population with “low-risk” of developing cancer. Chemoprevention, by definition, is a strategy for pharmacological intervention with naturally occurring and/or synthetic compounds that may prevent, inhibit or reverse carcinogenesis or suppress the development of invasive cancer (Sporn and Suh, 2002). The expanded definition of cancer chemoprevention is to inhibit or delay the development of neoplasia by blocking neoplastic inception as well as reversing the progression of transformed cells before the appearance of malignant lesions (Shukla and Gupta, 2005). In recent years, cancer chemoprevention has matured substantially and has been increasingly recognized by National Cancer Institute (NCI) prevention branch, American Society of Clinical Oncology (ASCO), American Cancer Society (ACS), American Association for Cancer Research (AACR) and some private foundations such as American Institute for Cancer Research (AICR) and Cancer Research and Prevention Foundation (CRPF). The development of chemopreventive agents is the major objective of the Chemoprevention Branch of the Division of Cancer Prevention (DCP) at NCI. The NCI-DCP aims to develop and implement research through clinical trials, screening and testing of new agents and identification of surrogate endpoint markers or cancer incidence reduction. The NCI also supports small- and large-scale clinical trials for this purpose. The overall goals of these programs are to achieve reduction in cancer incidence and mortality as well as to improve the quality of life in high- and low-risk individuals.
Section snippets
Cancer chemoprevention
Successful implementation of chemoprevention depends on a mechanistic understanding of carcinogenesis at the molecular, cellular and tissue levels. Carcinogenesis is a multi-step, multi-path and multi-focal process which involves a series of epigenetic and genetic alterations that begin with genomic instability and end with the development of cancer. At the molecular level, this process involves activation of oncogenes, loss of function of tumor suppressor genes, modulation in genes related to
Prostate cancer chemoprevention—clinical trials
Prostate cancer represents in many ways an ideal candidate for chemoprevention because of its high incidence and long latency period before the development of clinically evident disease (Klein, 2005). A large group of men who have a negative biopsy for prostate cancer but have rising PSA levels are advised for ‘watchful waiting’ and are turning to clinicians to find out steps to reduce the risk of being affected by the disease. Appropriate evidence-based studies are needed to test the efficacy
Conclusions
In recent years, there has been a great deal of research directed at the prevention of prostate cancer. The recent completed prevention trial on prostate cancer (PCPT) suggests that long-term preventive use of biologically active agents may be associated with unforeseen and possibly adverse biological effects. Clearly the risks and side-effects of chemopreventive agents must be weighed carefully against the potential cancer preventive benefits. The PCPT trial emphasizes that cancer
Future prospects
The future of cancer chemoprevention will be based on continuing progress in discovering and implementing these approaches in the following areas:
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Development of agents that precisely target molecular events involved in carcinogenesis.
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The discovery of new agents which are effective, safe, free of undesirable side-effects and usable over relatively long periods of time.
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The coordinated efforts of scientists, biotechnologist, geneticists and physicians in advancing this area of investigation.
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Better
Acknowledgments
This review is dedicated to my mentor Dr. Hasan Mukhtar to commemorate his 60th birthday. I will always remain thankful to him for his constant support and encouragement to further my career.
References (30)
- et al.
REDUCE Study Group. Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial
J. Urol.
(2004) - et al.
A prospective clinical trial of green tea for hormone refractory prostate cancer: an evaluation of the complementary/alternative therapy approach
Urol. Oncol.
(2005) The chemopreventive agent development research program in the Division of Cancer Prevention of the US National Cancer Institute: an overview
Eur. J. Cancer
(2005)- et al.
Cyclooxygenase-2 and prostate carcinogenesis
Cancer Lett.
(2003) - et al.
Phase IIA clinical trial to test the efficacy and safety of toremifene in men with high-grade prostatic intraepithelial neoplasia
Clin. Prostate Cancer
(2003) - et al.
Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study
Cancer Res.
(2006) - et al.
Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial
Br. J. Urol.
(1998) - et al.
Does high soy milk intake reduce prostate cancer incidence? The Adventist Health Study (United States)
Cancer Causes Control
(1998) - et al.
A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma
Cancer
(2003) - et al.
Protective effect of green tea against prostate cancer: a case–control study in southeast China
Int. J. Cancer
(2004)
Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health
Exp. Biol. Med.
A prospective study of lycopene and tomato product intake and risk of prostate cancer
Cancer Epidemiol., Biomarkers Prev.
Can prostate cancer be prevented?
Nat. Clin. Pract. Urol.
Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy
Cancer Epidemiol., Biomarkers Prev.
Effects of lycopene supplementation in patients with localized prostate cancer
Exp. Biol. Med.
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