Chemoprevention of colorectal cancer.
Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.
Gwyn
Karin
K
Department of Gastrointestinal Medicine and Nutrition, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Sinicrope
Frank A
FA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D017610:Calcium Compounds / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D004043:Dietary Fiber / Q000008:administration & dosage; D019587:Dietary Supplements; D000518:Eflornithine / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene / Q000008:administration & dosage
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017610:Calcium Compounds; D004043:Dietary Fiber; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019207:beta Carotene; D014810:Vitamin E; D014580:Ursodeoxycholic Acid; D005492:Folic Acid; D001205:Ascorbic Acid; D000518:Eflornithine