title: Cyclooxygenase as a target for colorectal cancer chemoprevention.
abstract: Colorectal cancer (CRC) is one of the most common neoplasia in Western countries and the second leading cause of cancer-related death. The vast majority of cases belong to sporadic forms, whereas a small but relevant proportion of them corresponds to inherited disorders, i.e. familial adenomatous polyposis and Lynch syndrome. These individuals with germline mutations in cancer-promoting genes, along with those who had already developed a colorectal neoplasm, either adenoma or carcinoma, stand to benefit from chemopreventive interventions. A large body of evidence indicates that the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) can reduce the risk of CRC. Experimental studies have demonstrated that these drugs decrease the incidence of carcinogen-induced colon tumors in rodents, and several epidemiological investigations and therapeutic trials have also shown a 40-50% reduction in the risk of colorectal adenoma and cancer in individuals taking NSAIDs. Moreover, patients with familial adenomatous polyposis taking sulindac or celecoxib experience a reduction in adenoma size and number. The chemopreventive effects of NSAID are largely related to inhibition of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase that catalyzes the conversion of arachidonic acid to prostaglandins. COX-2 overexpression is a frequent, but not universal event in colorectal neoplasms. Indeed, approximately 50% of adenomas and 80% of CRC express high levels of COX-2 mRNA and protein in neoplastic tissue. In this article, we will review the role of cyclooxygenase as a target for CRC chemoprevention, with special attention to the use of selective and non-selective COX-2 inhibitors in both individuals genetically predisposed and those who have already developed a colorectal neoplasm.
authors.affiliation: Gastroenterology Department,Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Catalonia, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreira
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
mesh_terms: D000236:Adenoma / Q000517:prevention & control; D011125:Adenomatous Polyposis Coli / Q000517:prevention & control; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods / Q000639:trends*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000517:prevention & control; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases