The role of COX-2 in intestinal cancer

C. S. Williams, R. L. Shattuck-Brandt, R. N. DuBois

Research output: Contribution to journalReview article

25 Scopus citations

Abstract

Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis, is transcribed from two distinct genes. COX-1 is expressed constitutively in most tissues whereas COX-2 is induced by a wide variety of stimuli and was initially identified as an immediate-early growth response gene. In addition, COX-2 expression is markedly increased in 85-90% of human colorectal adenocarcinomas while COX-1 levels remain unchanged. Several epidemiological studies have reported a 40-50% reduction in the risk of developing colorectal cancer in persons who chronically take non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, which are classic inhibitors of COX. Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumour multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX-2 contributes to the development of intestinal tumours and that inhibition of COX is chemopreventative. It is hoped that the chemopreventative effects of NSAIDs will be enhanced by the recent development of COX-2-specific inhibitors.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalExpert Opinion on Investigational Drugs
Volume8
Issue number1
DOIs
StatePublished - Jan 11 1999

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Keywords

  • Chemopreventative
  • Colorectal carcinoma
  • Cyclooxygenase
  • Non-steroidal anti-inflammatory drugs
  • Prostaglandins

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Williams, C. S., Shattuck-Brandt, R. L., & DuBois, R. N. (1999). The role of COX-2 in intestinal cancer. Expert Opinion on Investigational Drugs, 8(1), 1-12. https://doi.org/10.1517/13543784.8.1.1