Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2.
Two events in the last decade have set the stage for the large-scale clinical testing of chemopreventive agents for colorectal cancer in people at low to moderate risk for this disease. One of these is the discovery of a cause-effect relationship between the activities of cyclooxygenases (COX) and carcinogenesis in the colon, which can be interdicted by inhibitors of the enzymes. The other is the development of selective inhibitors of COX-2. These agents, when used in animals, also inhibit carcinogenesis in the colon. Additionally, they appear to be safe enough in humans to allow large-scale testing in healthy people. We review the key data implicating a causal relationship between the activity of COX and carcinogenesis and its possible mechanisms of action. We also emphasize work that points to other molecular targets for chemoprevention of colorectal cancer, which is emerging from studies of the link between COX and carcinogenesis.
Dannenberg
A J
AJ
Department of Medicine, The New York Hospital-Cornell Medical Center and Strang Cancer Prevention Center, NY 10021, USA.
Zakim
D
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases