Is COX-2 a 'collateral' target in cancer prevention?

Biochem Soc Trans. 2005 Aug;33(Pt 4):724-7. doi: 10.1042/BST0330724.


NSAIDs (non-steroidal anti-inflammatory drugs) prevent colon and other cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug-developmental work focusing on COX (cyclo-oxygenase) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, one COX-2 inhibitor has been withdrawn from the market because of cardiovascular side effects, and there are concerns about a class effect. Evidence suggests that COX-2 may not be the only, or the ideal, target for cancer prevention; for example, COX-2 is not expressed in human aberrant crypt foci, the earliest recognizable pre-malignant lesion in the colon; COX-2 is expressed in less than half of the adenomas; in vitro data show that NSAIDs do not require the presence of COX-2 to prevent cancer; in familial adenomatous polyposis, the COX-2 inhibitor, celecoxib, had a modest effect, which was weaker than that of a traditional NSAID; and COX-2-specific inhibitors have several COX-2-independent activities, which may account for part of their cancer-preventive properties. The multiple COX-2-independent targets, and the limitations of COX-2 inhibitors, suggest the need to explore targets other than COX-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenomatous Polyposis Coli / prevention & control
  • Anticarcinogenic Agents / therapeutic use*
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Epoprostenol / metabolism
  • Humans
  • Lactones / therapeutic use
  • Sulfones / therapeutic use


  • Anticarcinogenic Agents
  • Cyclooxygenase Inhibitors
  • Lactones
  • Sulfones
  • rofecoxib
  • Epoprostenol