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TWO ISOFORMS: There are two isoforms of cyclooxygenase (COX) with similar structure and metabolic activity. COX-1 is a constitutional enzyme. COX-2 is an inductible form. CYCLOOXYGENASE-1: COX-1 is present in most tissues, particularly in the kidney, the digestive tract mucosa, platelets, brain, liver and spleen. CYCLOOXYGENASE-2: COX-2 expression can be induced by an inflammatory process. Implicated in the development of certain cancers, COX-2 is expressed in numerous tumor cell lines and in most epithelial carcinomas. COX-2 favors tumor invasion and inhibits apoptosis. When it is absent, tumor growth is slower or stopped.

DISTINCT EFFECTS: Since the discovery of the two isoforms of COX, the therapeutic effects of nonsteroidal antiinflammatory drugs (NSAID) can be distinguished from their adverse effects linked to the inhibition of the constitutional form via selective inhibition of the inducible form. Non-selective NSAID that inhibit both COX isoforms are difficult to use for long-term regimens. NSAID AND CANCER PREVENTION: Epidemiology studies and animal and in vitro studies have demonstrated that regular use of NSAID reduced the incidence of colorectal cancer and certain precancer lesions. PROMISING PERSPECTIVES: COX-2 specific inhibitors, for example cerecoxib or rofecoxib, are potentially interesting for human therapy for chemoprevention of epithelial cancer or as medical treatment, alone or in combination with other anticancer treatments.

CYCLOOXYGENASE PATHWAY: Among the 3 metabolic pathways leading to oxidation of arachidonic acid, the cyclooxygenase (COX) pathway produces prostaglandin G2 that is rapidly transformed into prostaglandin H2. PROSTAGLANDINS: Prostaglandins are inflammation mediators that are strongly implicated in tumorgenesis. They participate in tumor initiation, promotion and growth. INFLAMMATION AND EPITHELIAL CANCER: Chronic inflammation is a risk factor for epithelial cancer. It induces prostaglandin synthesis via activation of COX-2. There is a cause and effect relationship between chronic inflammation and carcinogeneis via COX-2 expression. It has been demonstrated that COX-2 favors tumor invasion and inhibits apoptosis. Tumor growth is favored by PGE2-induced reduction in immunity; COX-2 inhibitors reinforce the immune response. Finally COX-2 is expressed in tumor neovessels and plays a role in angiogenesis.