Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors |
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| Authors: | Stanislav Kalinin Anna Malkova Tatiana Sharonova Vladimir Sharoyko Alexander Bunev Claudiu T Supuran Mikhail Krasavin |
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| Affiliation: | 1.Institute of Chemistry, Saint Petersburg State University, 199034 Saint Petersburg, Russia; (A.M.); (T.S.); (V.S.); (M.K.);2.School of Pharmacy, University of Eastern Finland, 70211 Kuopio, Finland;3.Medicinal Chemistry Center, Togliatti State University, 445020 Togliatti, Russia;4.Neurofarba Department, Universita degli Studi di Firenze, 50019 Florence, Italy; |
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| Abstract: | Combination therapy is becoming imperative for the treatment of many cancers, as it provides a higher chance of avoiding drug resistance and tumor recurrence. Among the resistance-conferring factors, the tumor microenvironment plays a major role, and therefore, represents a viable target for adjuvant therapeutic agents. Thus, hypoxia and extracellular acidosis are known to select for the most aggressive and resilient phenotypes and build poorly responsive regions of the tumor mass. Carbonic anhydrase (CA, EC 4.2.1.1) IX isoform is a surficial zinc metalloenzyme that is proven to play a central role in regulating intra and extracellular pH, as well as modulating invasion and metastasis processes. With its strong association and distribution in various tumor tissues and well-known druggability, this protein holds great promise as a target to pharmacologically interfere with the tumor microenvironment by using drug combination regimens. In the present review, we summarized recent publications revealing the potential of CA IX inhibitors to intensify cancer chemotherapy and overcome drug resistance in preclinical settings. |
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| Keywords: | carbonic anhydrase IX small-molecule inhibitors solid tumors tumor hypoxia tumor acidosis combination cancer therapy adjuvant agents |
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