Carbonic Anhydrase IX Inhibitors as Candidates for Combination Therapy of Solid Tumors

International Journal of Molecular Sciences

Tatiana Sharonova¹  Vladimir Sharoyko¹  Anna Malkova¹  Stanislav Kalinin¹  Mikhail Krasavin¹  Alexander Bunev²  Claudiu T. Supuran³ 

[1] Institute of Chemistry, Saint Petersburg State University, 199034 Saint Petersburg, Russia;Medicinal Chemistry Center, Togliatti State University, 445020 Togliatti, Russia;Neurofarba Department, Universita degli Studi di Firenze, 50019 Florence, Italy;

关键词: carbonic anhydrase IX;    small-molecule inhibitors;    solid tumors;    tumor hypoxia;    tumor acidosis combination cancer therapy;    adjuvant agents;   

DOI  :  10.3390/ijms222413405

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown