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Metabolites 2018, 8(1), 19; doi:10.3390/metabo8010019

Carbonic Anhydrases: Role in pH Control and Cancer

University of Florida, College of Medicine, Department of Biochemistry and Molecular Biology, P.O. Box 100245, Gainesville, FL 32610, USA
Authors to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 8 February 2018 / Accepted: 22 February 2018 / Published: 28 February 2018
(This article belongs to the Special Issue Carbonic Anhydrases and Metabolism)
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The pH of the tumor microenvironment drives the metastatic phenotype and chemotherapeutic resistance of tumors. Understanding the mechanisms underlying this pH-dependent phenomenon will lead to improved drug delivery and allow the identification of new therapeutic targets. This includes an understanding of the role pH plays in primary tumor cells, and the regulatory factors that permit cancer cells to thrive. Over the last decade, carbonic anhydrases (CAs) have been shown to be important mediators of tumor cell pH by modulating the bicarbonate and proton concentrations for cell survival and proliferation. This has prompted an effort to inhibit specific CA isoforms, as an anti-cancer therapeutic strategy. Of the 12 active CA isoforms, two, CA IX and XII, have been considered anti-cancer targets. However, other CA isoforms also show similar activity and tissue distribution in cancers and have not been considered as therapeutic targets for cancer treatment. In this review, we consider all the CA isoforms and their possible role in tumors and their potential as targets for cancer therapy. View Full-Text
Keywords: tumors; pH; carbonic anhydrases; metalloenzymes; carbonic anhydrase IX; carbonic anhydrase XII; cancer therapeutics; metabolism; tumor microenvironment; drug discovery tumors; pH; carbonic anhydrases; metalloenzymes; carbonic anhydrase IX; carbonic anhydrase XII; cancer therapeutics; metabolism; tumor microenvironment; drug discovery

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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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Mboge, M.Y.; Mahon, B.P.; McKenna, R.; Frost, S.C. Carbonic Anhydrases: Role in pH Control and Cancer. Metabolites 2018, 8, 19.

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