Cyclooxygenase (COX) is an enzyme complex that plays an important role in the conversion of arachidonic acid to prostaglandins. Prostaglandins are essential modulators of signal transduction pathways, which contribute to the metastatic properties of gastrointestinal (GI) malignancies. Although COX‐1 is constitutively active, COX‐2 is upregulated by cytokines, growth factors, and mitogen. COX‐2 is involved in malignant cell proliferation, angiogenesis, migration, invasion, and antiapoptotic activity. Thus, COX‐2 inhibitors may represent a promising therapeutic strategy for the treatment of GI cancers. In this review, the role of COX‐2 in GI cancers is explored, and its clinical applications as a therapeutic target are discussed.
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