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Molecules 2015, 20(2), 2323-2348; doi:10.3390/molecules20022323

Targeting Carbonic Anhydrase IX Activity and Expression

Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 18 August 2014 / Accepted: 25 December 2014 / Published: 30 January 2015
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Abstract

Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer. View Full-Text
Keywords: carbonic anhydrase IX; tumor hypoxia; prodrug; sulfonamide; RNAi-technology; cancer carbonic anhydrase IX; tumor hypoxia; prodrug; sulfonamide; RNAi-technology; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mahon, B.P.; Pinard, M.A.; McKenna, R. Targeting Carbonic Anhydrase IX Activity and Expression. Molecules 2015, 20, 2323-2348.

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