Targeting cyclooxygenase-2 for chemoprevention of inflammation-associated intestinal carcinogenesis: An update

Biochem Pharmacol. 2024 Oct:228:116259. doi: 10.1016/j.bcp.2024.116259. Epub 2024 May 3.

Abstract

Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. Cyclooxygenase-2 (COX-2) is a key enzyme involved in inflammatory signaling. While being transiently upregulated upon inflammatory stimuli, COX-2 has been found to be consistently overexpressed in human colorectal cancer and several other malignancies. The association between chronic inflammation and cancer has been revisited: cancer can arise when inflammation fails to resolve. Besides its proinflammatory functions, COX-2 also catalyzes the production of pro-resolving as well as anti-inflammatory metabolites from polyunsaturated fatty acids. This may account for the side effects caused by long term use of some COX-2 inhibitory drugs during the cancer chemopreventive trials. This review summarizes the latest findings highlighting the dual functions of COX-2 in the context of its implications in the development, maintenance, and progression of cancer.

Keywords: Chemoprevention; Cyclooxygenase-2; Inflammation; Non-resolving inflammation; Resolution of inflammation.

Publication types

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

MeSH terms

  • Animals
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Chemoprevention / methods
  • Chemoprevention / trends
  • Cyclooxygenase 2 Inhibitors* / pharmacology
  • Cyclooxygenase 2 Inhibitors* / therapeutic use
  • Cyclooxygenase 2* / metabolism
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Inflammation* / prevention & control
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / prevention & control

Substances

  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors