Cyclooxygenase 2 (COX-2) as a target for therapy and noninvasive imaging.
Prostaglandins modulate a wide range of biologic functions, including wound healing, temperature regulation, reproduction, and many aspects of immune function. Exaggerated production of prostaglandins contributes to a large number pathophysiologies. The critical enzyme in prostaglandin biosynthesis is prostaglandin synthase, also known as cyclooxygenase (COX). The nonsteroidal anti-inflammatory drugs (NSAIDs), one of the largest classes of pharmaceutical agents, exert most of their biologic effects by inhibiting cyclooxygenase production of prostaglandins. The discovery of a second, inducible form of cyclooxygenase, now known as COX-2, responsible for the production of prostaglandins in most pathological states, revived a relatively moribund research area in biochemistry, physiology, and pharmacology, and led to the search for and discovery of a new class of pharmacologic agents. The coxibs have greater efficacy and substantially ameliorated side effects when compared to the classic NSAIDs. Because of the pervasive role of COX-2 in a wide range of human pathologies, the coxibs have been the most successful entry into the pharmaceutical market in history, responsible for 6-10 billion dollars in sales annually. The ability to noninvasively monitor COX-2 expression with molecular imaging probes will provide a corresponding advance in diagnosing COX-2-based disease, monitoring progression of such diseases, and evaluating alternative therapies.
Herschman
Harvey R
HR
Department of Biological Chemistry, Jonsson Comprehensive Cancer Center, and Molecular Biology Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. hherschman@mednet.ucla.edu
Talley
John J
JJ
DuBois
Raymond
R
D000818:Animals; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012756:Sheep
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases