Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?
COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.
Doherty
Glen A
GA
Beaumont Hospital, Department of Gastroenterology, Beaumont Road, Dublin, D8, Ireland. glen_doherty@hotmail.com
Murray
Frank E
FE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D051546:Cyclooxygenase 2