Cyclooxygenase 2 selective inhibitors in cancer treatment and prevention

Prostaglandin synthesis by a number of enzymes is important at all stages during the genesis of cancer. The availability of prostaglandin H(2) as a substrate for prostaglandin production is a critical control point in its synthesis. Cyclooxygenase (COX) occurs in two forms (COX-1 and -2) and acts as the rate-limiting enzyme that generates prostaglandin H(2). COX-1 is produced as a steady-state enzyme, while COX-2 is heavily involved in inflammation and tumorigenesis. Differences in the catalytic sites of these enzymes are utilised to generate COX-2 selective inhibitors. Certain chemical characteristics of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors make some of these inhibitors more effective against COX-2 than others. Epidemiological, animal and preclinical data demonstrate the promise of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors as anticancer agents. Ongoing clinical trials are designed to determine the efficacy of non-steroidal anti-inflammatory drugs and COX-2 selective inhibitors in the prevention and treatment of many types of cancer.