Cyclo-oxygenase-2 inhibitors in colorectal cancer prevention

Menachem Moshkowitz, Nadir Arber

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalAmerican Journal of Cancer
Volume5
Issue number6
DOIs
StatePublished - 2006

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