Prospects in NSAID-derived chemoprevention of colorectal cancer

Biochem Soc Trans. 2005 Aug;33(Pt 4):667-71. doi: 10.1042/BST0330667.

Abstract

There is strong evidence for an important role for increased COX (cyclo-oxygenase)-2 expression and PG (prostaglandin) E2 production in colorectal tumorigenesis. PGE(2) acts through four E-prostanoid receptors (EP1-4). COX-2 has therefore become a target for the potential chemoprevention and therapy of colorectal cancer. However, any therapeutic/preventive strategy has the potential to have an impact on physiological processes and hence result in side effects. General COX (COX-1 and -2) inhibition by traditional NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin, although chemopreventive, has some side effects, as do some conventional COX-2-selective NSAIDs. As PGE2 is thought to be the major PG species responsible for promoting colorectal tumorigenesis, research is being directed to a number of protein targets downstream of COX-2 that might allow the selective inhibition of the tumour-promoting activities of PGE2, while minimizing the associated adverse events. The PGE synthases and E-prostanoid receptors (EP1-4) have therefore recently attracted considerable interest as potential novel targets for the prevention/therapy of colorectal cancer. Selective (and possibly combinatorial) inhibition of the synthesis and signalling of those PGs most highly associated with colorectal tumorigenesis may have some advantages over COX-2-selective inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anticarcinogenic Agents / therapeutic use*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / prevention & control*
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Humans
  • Incidence
  • Models, Biological
  • Receptors, Prostaglandin E / physiology
  • Receptors, Prostaglandin E, EP1 Subtype

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Cyclooxygenase Inhibitors
  • PTGER1 protein, human
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype