Prostaglandins and COX-2: Role in antiangiogenic therapy

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 antiinflammatory 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.