COX-2 inhibition and prevention of cancer

Abstract

The potential for cyclo-oxygenase inhibition in cancer prevention and treatment is founded on epidemiology (reduction of colorectal cancer in aspirin users), animal experiments and molecular genetics. Trials using the NSAID sulindac also reduced the number of polyps in patients with familial adenomatous polyposis, but the well-known gastrointestinal toxic effects of aspirin and NSAIDs have discouraged the exploitation of their antineoplastic potential. The advent of specific COX-2 inhibitors, which do not interfere with the cytoprotective constitutive COX-1 enzyme, and the demonstration of increased COX-2 expression in many common malignancies beside colorectal cancer, has opened up new therapeutic possibilities. Recently a non-cyclo-oxygenase effect of COX-2 inhibitors, which combines the PPARδ and the APC tumour suppressor activity, was also demonstrated. The selective COX-2 inhibitor celecoxib has been approved by the FDA for adjuvant treatment of familial adenomatous polyposis, and a large number of prevention and treatment trials of colorectal and other common cancers (prostate and breast cancer) have been started.