Potential role of selective COX-2 inhibitors in cancer management.
Tumorigenesis is a complex process, and understanding the mechanisms behind tumorigenesis is key to identifying effective targeted therapies. Prostaglandins are signaling lipophilic molecules derived from phospholipids that are involved in normal physiologic functions. However, overexpression of prostaglandins has been associated with tumorigenesis. Several epidemiologic studies have shown an inverse correlation between the incidence of colon cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis. The NSAIDs target cyclooxygenases (COX), essential enzymes inprostaglandin production. Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that is usually not expressed in normal tissue. Because COX-2 is frequently overexpressed in premalignant lesions and neoplasms, specific COX-2 inhibitors have been investigatedas chemoprevention andpotential chemotherapeutic agents. There is now preclinical and early clinical data that suggest inhibitors of COX-2 may protect against colon, breast, lung, esophageal, and oral tumors. This paper will discuss evidence addressing the possible mechanistic contribution of COX-2 in tumorigenesis and will explore the link between COX-2 activity and carcinogenesis. The potential role of COX-2 inhibitors in the chemoprevention and treatment of various tumors will also be discussed. Clinical trials using targeted inhibitors of COX-2 will be critical in determining if COX-2 is a viable molecular target in cancer management.
Dang
Chau T
CT
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. dangc@mskcc.org
Shapiro
Charles L
CL
Hudis
Clifford A
CA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases
D000894:Anti-Inflammatory Agents, Non-Steroidal; 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