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Michael J. Thun, S. Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs NSAIDs , particularly the highly selective cyclooxygenase COX -2 inhibitors, have promise as anticancer agents. NSAIDs restore normal apoptosis in human adenomatous colorectal polyps and in various cancer cell lines that have lost adenomatous polyposis coli gene function. NSAIDs also inhibit angiogenesis in cell culture and rodent models of angiogenesis. Many epidemiologic studies have found that long-term use of NSAIDs is associated with a lower risk of colorectal cancer, adenomatous polyps, and, to some extent, other cancers. Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis FAP. However, unresolved questions about the safety, efficacy, optimal treatment regimen, and mechanism of action of NSAIDs currently limit their clinical application to the prevention of polyposis in FAP patients. Moreover, the development of safe and effective drugs for chemoprevention is complicated by the potential of even rare, serious toxicity to offset the benefit of treatment, particularly when the drug is administered to healthy people who have low annual risk of developing the disease for which treatment is intended. This review considers generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention. We critically examine the published experimental, clinical, and epidemiologic literature on NSAIDs and cancer, especially that regarding colorectal cancer, and identify strategies to overcome the various logistic and scientific barriers that impede clinical trials of NSAIDs for cancer prevention. 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It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign in through your institution. JNCI Portfolio. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Journal Article. Thun , Michael J. Correspondence to: Michael J. Thun, M. Oxford Academic. Google Scholar. Jane Henley. Carlo Patrono. Revision received:. Cite Cite Michael J. Select Format Select format. Permissions Icon Permissions. Abstract Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs NSAIDs , particularly the highly selective cyclooxygenase COX -2 inhibitors, have promise as anticancer agents. Issue Section:. You do not currently have access to this article. Download all slides. Sign in Get help with access. Institutional access Sign in through your institution Sign in through your institution. 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