Nonsteroidal anti-inflammatory drugs and colorectal cancer: Evolving concepts of their chemopreventive actions

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N'onsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceutical compounds worldwide. Since it was recognized that certain plant constituents, such as the bark of the white willow (Salix alba vulgaris), were helpful in the treatment of fever, inflammatory diseases, and other maladies, they have been systematically exploited by humankind. Modern medicine has witnessed the isolation of salicin, the active ingredient of the willow bark; the synthesis of sodium salicylate; the formulation of aspirin (acetylsalicylic acid) in 1897; and finally the introduction of indomethacin, the first of many nonsalicylate NSAIDs, in 1963. In the last few years, new uses for these compounds have been recognized such as in the prevention and management of atherosclerotic vascular diseases. NSAIDs have recently been discovered to have antineoplastic properties, particularly in the gastrointestinal tract.l'2 Strong evidence suggests that they prevent colorectal cancer in the general population, and some of them cause regression of adenomatous polyps in patients with familial adenomatous polyposis (FAP)3; very recently, preliminary data indicate that the NSAID sulindac can also cause regression of sporadic adenomas. 4 This Viewpoints article reviews the evidence for the chemopreventive and antineoplastic activity of NSAIDs and discusses the mechanisms by which their remarkable effects occur. NSAIDs Are Antineoplastic: The Evidence That NSAIDs are antineoplastic, prominently in the colon, is derived from three lines of evidence: animal studies, clinical studies and case reports, and epidemiological data.