TY - JOUR
T1 - Cyclo-oxygenase-2 inhibitors in colorectal cancer prevention
AU - Moshkowitz, Menachem
AU - Arber, Nadir
N1 - Funding Information:
N. Arber has performed consultancies for G.I. View Ltd, Israel, owns stock and has received honoria from Pfizer, USA, and has received grants from Pfizer, USA and Merck, USA. No sources of funding were used to assist in the preparation of this review.
PY - 2006
Y1 - 2006
N2 - Previous experimental epidemiologic and clinical studies have shown a significant reduction in colorectal cancer occurrence and mortality among individuals taking NSAIDs. NSAIDs inhibit the enzymatic activity of both isoforms of cyclo-oxygenase (COX-1 and COX-2), which regulate prostaglandin synthesis. COX-2 is an inducible enzyme that is overexpressed at sites of inflammation and in several epithelial cancers. Several studies have indicated that COX-2 overexpression appears to be involved in tumorigenesis by promoting cell division and proliferation, inhibiting apoptosis, stimulating angiogenesis, altering cell adhesion, and enhancing tumor cell invasiveness. Blocking of these activities by COX-2 selective inhibitors is considered the main mechanism that explains the anticarcinogenic effect of COX-2 selective inhibitors. In addition, other independent COX-2 mechanisms have been described. Treatment with selective COX-2 inhibitors has shown promising results in the suppression of colon polyps, both in animal models for familial adenomatous polyposis (FAP) and in patients with FAP, and recent clinical studies have identified the potential benefit of these agents for colon cancer chemoprevention. However, serious concerns have been raised regarding the potential adverse effects of long-term selective COX-2 inhibitor use, most notably those within the cardiovascular system, such as myocardial infarctions, strokes, and increased blood pressure. The role of COX-2 inhibitors in cancer chemoprevention is still evolving and a careful risk/benefit analysis of the recent clinical studies would mandate the precise clinical setting that these drugs can be used in.
AB - Previous experimental epidemiologic and clinical studies have shown a significant reduction in colorectal cancer occurrence and mortality among individuals taking NSAIDs. NSAIDs inhibit the enzymatic activity of both isoforms of cyclo-oxygenase (COX-1 and COX-2), which regulate prostaglandin synthesis. COX-2 is an inducible enzyme that is overexpressed at sites of inflammation and in several epithelial cancers. Several studies have indicated that COX-2 overexpression appears to be involved in tumorigenesis by promoting cell division and proliferation, inhibiting apoptosis, stimulating angiogenesis, altering cell adhesion, and enhancing tumor cell invasiveness. Blocking of these activities by COX-2 selective inhibitors is considered the main mechanism that explains the anticarcinogenic effect of COX-2 selective inhibitors. In addition, other independent COX-2 mechanisms have been described. Treatment with selective COX-2 inhibitors has shown promising results in the suppression of colon polyps, both in animal models for familial adenomatous polyposis (FAP) and in patients with FAP, and recent clinical studies have identified the potential benefit of these agents for colon cancer chemoprevention. However, serious concerns have been raised regarding the potential adverse effects of long-term selective COX-2 inhibitor use, most notably those within the cardiovascular system, such as myocardial infarctions, strokes, and increased blood pressure. The role of COX-2 inhibitors in cancer chemoprevention is still evolving and a careful risk/benefit analysis of the recent clinical studies would mandate the precise clinical setting that these drugs can be used in.
UR - http://www.scopus.com/inward/record.url?scp=33846866994&partnerID=8YFLogxK
U2 - 10.2165/00024669-200605060-00002
DO - 10.2165/00024669-200605060-00002
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AN - SCOPUS:33846866994
VL - 5
SP - 357
EP - 362
JO - American Journal of Cancer
JF - American Journal of Cancer
SN - 1175-6357
IS - 6
ER -