ABSTRACT
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Several lines of evidence suggest that cyclooxygenase-2 (COX-2) is a rational target for
anticancer therapy. Epidemiologic data have shown that chronic use of nonsteroidal anti-
inflammatory agents (NSAIDs) reduce the risk of a number of solid malignancies, including
colorectal and esophageal carcinoma.1 NSAIDs inhibit cyclooxygenase, a family of enzymes
critical for arachidonic acid metabolism (Figure 11.1).2 The cyclooxygenase enzymes convert
arachidonic acid to prostaglandin H2 (PGH2) and subsequently thromboxane (TXA2) and
prostaglandins PGE2, PGF2, PGD2, and PGI2. 3 The constitutive cyclooxygenase-1 (COX-1)
isozyme is present in most normal tissues to control normal physiologic functions, including
maintenance of the gastrointestinal mucosa, regulation of renal blood flow, and platelet
aggregation. In contrast, the COX-2 enzyme isozyme inducible by cytokines and growth
factors is often present in inflammatory conditions and cancer.4
