Cancer chemoprevention: Successes and failures

BACKGROUND: Cancer has traditionally been considered a single disease, but it is now known to be far more complex, with an unfolding etiology. In less than 2 centuries, hundreds - if not thousands - of drugs for the treatment of cancer and for palliative care have been developed and tested, with 143 having achieved approval by the US Food and Drug Administration (Medi-Lexicon International; "Cancer Drugs & Oncology Drugs," http://www.medilexicon.com/drugs-list/cancer.php). Just 13 agents have been approved, however, for treating precancerous lesions or for reducing risk. CONTENT: Nonsteroidal antiinflammatory drugs, vitamins, food constituents and spice components, antidiabetic drugs, ω-3 fatty acids, and fiber are just a few of the many classes of compounds that have been tested for their cancer-preventive potential. We highlight some of the agents that have been scrutinized by way of randomized clinical trials in humans for their cancer prevention potential. We summarize the major definitive cancer chemoprevention studies that (a) were successful in demonstrating efficacy and ultimately received regulatory approval; (b) were not successful in demonstrating efficacy or had unacceptable toxicities, but from which the field has learned important lessons; and (c) showed compelling efficacy against surrogate end points but failed to achieve regulatory approval because of a lack of consensus regarding the relevance of those end points to clinical benefit. SUMMARY: Chemopreventive studies have provided new insights into early disease pathogenesis, stimulated new risk assessments and models, fostered important research in end point biomarkers, and led to 13 approved agents. The development of safe and effective chemopreventive agents holds tremendous potential for reducing the burden of cancer.