Prostaglandin E2 as a therapeutic target in bladder cancer: From basic science to clinical trials

Prostaglandins Other Lipid Mediat. 2020 Jun:148:106409. doi: 10.1016/j.prostaglandins.2020.106409. Epub 2020 Jan 10.

Abstract

Bladder cancer (BCa) is a common solid tumor marked by high rates of recurrence, especially in non-muscle invasive disease. Prostaglandin E2 (PGE2) is a ubiquitously present lipid mediator responsible for numerous physiological actions. Inhibition of cyclooxygenase (COX) enzymes by the non-steroidal anti-inflammatory (NSAID) class of drugs results in reduced PGE2 levels. NSAID usage has been associated with reductions in cancers such as BCa. Clinical trials using NSAIDs to prevent recurrence have had mixed results, but largely converge on issues with cardiotoxicity. The purpose of this review is to understand the basic science behind how and why inhibitors of PGE2 may be effective against BCa, and to explore alternate therapeutic modalities for addressing the role of PGE2 without the associated cardiotoxicity. We will address the role of PGE2 in a diverse array of cancer-related functions including stemness, immunosuppression, proliferation, cellular signaling and more.

Keywords: COX-2; Celecoxib; EP receptor; Immunosuppression; Inflammation; mPGES-1.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Clinical Trials as Topic
  • Cyclooxygenase 2 / chemistry*
  • Dinoprostone / metabolism*
  • Humans
  • Prostaglandin-E Synthases / antagonists & inhibitors*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2
  • Prostaglandin-E Synthases
  • Dinoprostone