Cyclooxygenase-2: A role in cancer stem cell survival and repopulation of cancer cells during therapy

Lisa Pang, Emma A. Hurst, David Argyle

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2), a major mediator of inflammation and angiogenesis. COX-2 is over-expressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour, and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects for resistant cancer cells that are able to reinitiate tumour growth. However there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology, and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.
Original languageEnglish
Article number2048731
JournalStem Cells International
Volume2016
Early online date1 Nov 2016
DOIs
Publication statusE-pub ahead of print - 1 Nov 2016

Keywords

  • COX-2
  • prostaglandin E2
  • Cancer stem cells
  • tumour repopulation
  • therapeutic-resistance

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