Chemoprevention of hereditary colon cancers: time for new strategies.
Colorectal cancer (CRC) is potentially preventable. Chemoprevention, a focus of research for the past three decades, aims to prevent or delay the onset of cancer through the regression or prevention of colonic adenomas. Ideal pharmacological agents for chemoprevention should be cheap and nontoxic. Although data indicate that aspirin can reduce the risk of CRC in the general population, the highest return from chemopreventive strategies would be expected in patients with the highest risk of developing the disease, particularly those with a defined hereditary predisposition. Despite compelling data showing that a large number of chemopreventive agents show promise in preclinical CRC models, clinical studies have yielded conflicting results. This Review provides a historical and methodological perspective of chemoprevention in familial adenomatous polyposis and Lynch syndrome, and summarizes the current status of CRC chemoprevention in humans. Our goal is to critically focus on important issues of trial design, with particular attention on the choice of appropriate trial end points, how such end points should be measured, and which patients are the ideal candidates to be included in a chemopreventive trial.
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, Bologna 40124, Italy.
Luigi
L
Ricciardiello
Department of Medicine, University of Colorado School of Medicine and Gastroenterology of the Rockies, 5001 E 17th Avenue Parkway, Denver, Colorado 80220, USA.
Dennis J
DJ
Ahnen
Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77054, USA.
Patrick M
PM
Lynch
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000235:genetics / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000517:prevention & control; D003474:Curcumin / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D055808:Drug Discovery; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D013467:Sulindac / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D015525:Fatty Acids, Omega-3; D013467:Sulindac; D003474:Curcumin; D001241:Aspirin