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Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors

Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy
Metabolites 2017, 7(3), 48; https://doi.org/10.3390/metabo7030048
Received: 31 August 2017 / Revised: 15 September 2017 / Accepted: 15 September 2017 / Published: 16 September 2017
(This article belongs to the Special Issue Carbonic Anhydrases and Metabolism)
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors. In this review, I will present the state of the art on the development of CA inhibitors (CAIs) targeting the tumor-associated CA isoforms, which may have applications for the treatment and imaging of cancers expressing them. Small molecule inhibitors, one of which (SLC-0111) completed Phase I clinical trials, and antibodies (girentuximab, discontinued in Phase III clinical trials) will be discussed, together with the various approaches used to design anticancer agents with a new mechanism of action based on interference with these crucial metabolites, protons and bicarbonate. View Full-Text
Keywords: tumor; metabolism; carbonic anhydrase; isoforms IX and XII; inhibitor; sulfonamide; antibody tumor; metabolism; carbonic anhydrase; isoforms IX and XII; inhibitor; sulfonamide; antibody
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Supuran, C.T. Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors. Metabolites 2017, 7, 48.

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