COX-2 inhibitors in cancer treatment and prevention, a recent development.

Epidemiological and experimental studies have demonstrated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of human cancers. NSAIDs block endogenous prostaglandin synthesis through inhibition of cyclooxygenase (COX) enzymatic activity. COX-2, a key isoenzyme in conversion of arachidonic acid to prostaglandins, is inducible by various agents such as growth factors and tumor promoters, and is frequently overexpressed in various tumors. The contribution of COX-2 to carcinogenesis and the malignant phenotype of tumor cells has been thought to be related to its abilities to (i) increase production of prostaglandins, (ii) convert procarcinogens to carcinogens, (iii) inhibit apoptosis, (iv) promote angiogenesis, (v) modulate inflammation and immune function, and (vi) increase tumor cell invasiveness, although some studies indicated that NSAIDs have COX-2-independent effects. A number of clinical trials using COX-2 inhibitors are in progress, and the results from these studies will increase our understanding of COX-2 inhibition in both cancer treatment and prevention. The combination of COX-2 inhibitors with radiation or other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Recent progress in the treatment and prevention of cancers of the colon, esophagus, lung, bladder, breast and prostate with NSAIDs, especially COX-2 inhibitors, is also discussed.