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.
Menter
David G
DG
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Box 236, 1515 Holcombe Boulevard, Houston, TX 77030, USA. dmenter@mdanderson.org
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001665:Binding Sites; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy*; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases