Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer

Research output: Contribution to journalArticle

77 Citations (Scopus)

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. A causal link for COX-2 in epithelial tumorigenesis was shown in genetically manipulated animal models of colon and breast carcinoma. Studies have elucidated the regulation of COX-2 expression and have identified EP receptors through which prostanoids exert their biological effects. Mechanistic studies indicated that COX-2 is involved in apoptosis resistance, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects in tumorigenesis. Furthermore, forced COX-2 expression has been shown to suppress apoptosis by modulating the level of death receptor 5 (DR5) and this effect was reversed by a COX inhibitor. COX enzymes are targets for cancer prevention as shown by the observation that nonselective COX and selective COX-2 inhibitors have been reported to effectively prevent experimental colon cancer and can regress colorectal polyps in patients with familial adenomatous polyposis. This review will focus on the role of COX-2 as a target for the prevention and treatment of human colorectal cancer.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalMolecular Carcinogenesis
Volume45
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Cyclooxygenase 2
Colorectal Neoplasms
Prostaglandins
Carcinogenesis
Therapeutics
TNF-Related Apoptosis-Inducing Ligand Receptors
Apoptosis
Neoplasms
Adenomatous Polyposis Coli
Cyclooxygenase 2 Inhibitors
Enzymes
Polyps
Colonic Neoplasms
Colon
Animal Models
Breast Neoplasms
Inflammation

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Targeting cyclooxygenase-2 for prevention and therapy of colorectal cancer. / Sinicrope, Frank A.

In: Molecular Carcinogenesis, Vol. 45, No. 6, 06.2006, p. 447-454.

Research output: Contribution to journalArticle

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