Counterpoint: From animal models to prevention of colon cancer. Criteria for proceeding from preclinical studies and choice of models for prevention studies.
Corpet and Pierre (D. E. Corpet and F. Pierre, Cancer Epidemiol. Biomark. Prev., 12: 391-400, 2003) have reviewed the prevention studies made with the azoxymethane rat and Min mouse colon cancer models, and have shown that many agents reduce the numbers of these experimental tumors. They suggest that agents with preventive activity with little or no toxicity should be evaluated in clinical intervention studies without delay. I think that the decision to proceed to a clinical trial is more complex, and involves an understanding of the safety of the agent and of the strength and consistency of the preclinical data. However, I am also impressed by the wide range of agents that have been found to affect the development of colon cancer in animals. This suggests that human colon cancer may be the consequence of many different dietary and lifestyle deficiencies, a view supported by the observation that normal mice develop colon cancer when fed diets deficient in several food components known to prevent tumors with the azoxymethane rat model [Newmark, H. L. et al., Carcinogenesis (Lond.), 22: 1871-1875, 2001]. There is a clear need to evaluate the preventive effects of additional combinations of these agents, identified perhaps from the Corpet and Pierre review (D. E. Corpet and F. Pierre, Cancer Epidemiol. Biomark. Prev., 12: 391-400, 2003), or from actual human high-risk diets. With diets that increase the risk of "spontaneous cancer" in hand, the stage would be set for assessing the most effective ways to reduce colon cancer risk, again first with animal studies, then clinical trials, and then perhaps population studies.
Bruce
W Robert
WR
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario M5S 3E2, Canada. wr.bruce@utoronto.ca
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D018890:Chemoprevention; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004032:Diet; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D051381:Rats
D016588:Anticarcinogenic Agents; D001397:Azoxymethane