Carbonic anhydrase inhibitors and the management of cancer.
Recent progress in understanding the role of catalytically active carbonic anhydrases in tumors has opened new possibilities for diagnostic and/or therapeutic applications of carbonic anhydrase inhibitors selectively blocking the enzyme activity of cancer-related isoforms, namely CA IX and CA XII. Different classes of inhibitors have been investigated in order to evaluate their usefulness as in vivo imaging tools, as modulators of intratumoral pH that influences uptake of conventional chemotherapeutics, or as drugs impeding survival of tumor cells exposed to physiological stresses including hypoxia and acidosis. Here we summarize the most important data related to expression, regulation and functional aspects of cancer-related carbonic anhydrases and discuss advances in synthesis and preclinical studies of isozyme-selective and highly efficient carbonic anhydrase inhibitors.
Pastorekova
Silvia
S
Center of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovakia. virusipa@savba.sk
Kopacek
Juraj
J
Pastorek
Jaromir
J
D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D020033:Protein Isoforms
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D002256:Carbonic Anhydrases