Role of cyclooxygenase-2 in colorectal cancer

Frank A. Sinicrope, Sharlene Gill

Research output: Contribution to journalReview article

158 Scopus citations

Abstract

Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.

Original languageEnglish (US)
Pages (from-to)63-75
Number of pages13
JournalCancer and Metastasis Reviews
Volume23
Issue number1-2
DOIs
StatePublished - Jan 1 2004

Keywords

  • Colorectal cancer
  • Coxibs
  • Cyclooxygenase-2
  • NSAIDs
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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