Journal
ONCOTARGET
Volume 3, Issue 1, Pages 84-97Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.422
Keywords
cancer; hypoxia; carbonic anhydrase IX; metastasis; targeted therapeutics
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Funding
- Canadian Institutes of Health Research (CIHR)
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Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness. Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecule inhibitors, consequently disrupting pH regulation by cancer cells, has been shown recently to impair primary tumor growth and metastasis. Many of these agents are in preclinical or clinical development and constitute a novel, targeted strategy for cancer therapy.
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