COX-2 inhibition and prevention of cancer

The potential for cyclo-oxygenase inhibition in cancer prevention and treat ment is founded on epidemiology (reduction of colorectal cancer in aspirin users), animal experiments and molecular genetics. Trials using the NSAID s ulindac also reduced the number of polyps in patients with familial adenoma tous polyposis, but the well-known gastrointestinal toxic effects of aspiri n and NSAIDs have discouraged the exploitation of their antineoplastic pote ntial. The advent of specific COX-2 inhibitors, which do not interfere with the cytoprotective constitutive COX-1 enzyme, and the demonstration of inc reased COX-2 expression in many common malignancies beside colorectal cance r, has opened up new therapeutic possibilities. Recently a non-cyclo-oxygen ase effect of COX-2 inhibitors, which combines the PPAR delta and the APC t umour suppressor activity, was also demonstrated. The selective COX-2 inhib itor celecoxib has been approved by the FDA for adjuvant treatment of famil ial adenomatous polyposis, and a large number of prevention and treatment t rials of colorectal and other common cancers (prostate and breast cancer) h ave been started.