COX-2 in cancer: Gordian knot or achilles heel?

Ioannis Stasinopoulos, Tariq Shah, Marie France Penet, Balaji Krishnamachary, Zaver M. Bhujwalla

Research output: Contribution to journalArticle

Abstract

The networks of blood and lymphatic vessels and of the extracellular matrix and their cellular and structural components, that are collectively termed the tumor microenvironment, are frequently co-opted and shaped by cancer cells to survive, invade, and form distant metastasis. With an enviable capacity to adapt to continually changing environments, cancer represents the epitome of functional chaos, a stark contrast to the hierarchical and organized differentiation processes that dictate the development and life of biological organisms. The consequences of changing landscapes such as hypoxia and acidic extracellular pH in and around tumors create a cascade of changes in multiple pathways and networks that become apparent only several years later as recurrence and metastasis. These molecular and phenotypic changes, several of which are mediated by COX-2, approach the complexities of a "Gordian Knot." We review evidence from our studies and from literature suggesting that cyclooxygenase-2 (COX-2) biology presents a nodal point in cancer biology and an "Achilles heel" of COX-2-dependent tumors.

Original languageEnglish (US)
Article numberArticle 34
JournalFrontiers in Pharmacology
Volume4 MAR
DOIs
StatePublished - Aug 20 2013

Keywords

  • COX-2 and HIF-1
  • COX-2 and LEF-1
  • COX-2 inhibitors
  • Cyclooxygenase 2
  • Inflammation and cancer
  • Inflammation and hypoxia
  • Invasion
  • Metastasis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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