Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors
AbstractHypoxia 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 188.8.131.52), 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
Share & Cite This Article
Supuran, C.T. Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors. Metabolites 2017, 7, 48.
Supuran CT. Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors. Metabolites. 2017; 7(3):48.Chicago/Turabian Style
Supuran, Claudiu T. 2017. "Carbonic Anhydrase Inhibition and the Management of Hypoxic Tumors." Metabolites 7, no. 3: 48.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.