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Molecular targets for chemoprevention: role in choosing and developing new agents

By William P. Steward

Abstract

This is the author's final draft of the paper published as European Journal of Cancer Supplements, 2007, 5(5), pp.388-390. The final published version is available on Science Direct, doi:10.1016/S1359-6349(07)70071-X.Introduction: The field of cancer chemoprevention has developed considerably over the past two decades with several large randomised trials having been undertaken. Some of these have been positive and have included a demonstration of the efficacy of tamoxifen to reduce the risk of breast cancer and finasteride to have an impact on prostate cancer incidence. Unfortunately several trials have been negative and some have even produced results suggesting a deleterious effect of the agent under investigation. Chemoprevention trials are, of necessity, usually very large and extremely costly. To date, one of the main methods for choosing agents to investigate in trials has been retrospective population-based analysis of an apparent association between ingestion of the agent and a reduced incidence of cancer. Unfortunately such analyses are often flawed by many sources of bias. In addition, adverse effects of exposure to such agents over a protracted period have not been anticipated. Successful chemoprevention requires an agent which has a significant impact on cancer risk but is also extremely safe and well tolerated. With the increasing understanding of molecular mechanisms leading to carcinogenesis, it is imperative that cancer preventive agents are developed more rationally and are targeted towards these mechanisms – both to increase efficacy and also to reduce the potential for toxicity. This article will highlight some of the more promising potential targets which can be used to choose and design drugs for testing as chemopreventive agents. The identification of targets could also enable the development of biomarkers to test efficacy during early clinical development

Publisher: Elsevier
Year: 2007
DOI identifier: 10.1016/S1359-6349(07)70071-X.
OAI identifier: oai:lra.le.ac.uk:2381/2692

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