TY - JOUR
T1 - COX-2 in cancer
T2 - Gordian knot or achilles heel?
AU - Stasinopoulos, Ioannis
AU - Shah, Tariq
AU - Penet, Marie France
AU - Krishnamachary, Balaji
AU - Bhujwalla, Zaver M.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - COX-2 and HIF-1
KW - COX-2 and LEF-1
KW - COX-2 inhibitors
KW - Cyclooxygenase 2
KW - Inflammation and cancer
KW - Inflammation and hypoxia
KW - Invasion
KW - Metastasis
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U2 - 10.3389/fphar.2013.00034
DO - 10.3389/fphar.2013.00034
M3 - Article
C2 - 23579438
AN - SCOPUS:84881538331
VL - 4 MAR
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
M1 - Article 34
ER -