title: COX-2 in cancer: Gordian knot or Achilles heel?
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.
authors.affiliation: Johns Hopkins University In-vivo Cellular and Molecular Imaging Center Program, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine Baltimore, MD, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stasinopoulos
authors.forename: Tariq
authors.initials: T
authors.lastname: Shah
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Penet
authors.forename: Balaji
authors.initials: B
authors.lastname: Krishnamachary
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
keywords: COX-2 and HIF-1; COX-2 and LEF-1; COX-2 inhibitors; cyclooxygenase 2; inflammation and cancer; inflammation and hypoxia; invasion; metastasis