Inhibition of carbonic anhydrase IX: a new strategy against cancer.
Of the thirteen active carbonic anhydrase (CA) isozymes, the transmembrane isoform CA IX has been shown to be linked with carcinogenesis. CA IX presents an ectopic expression in a multitude of carcinomas derived from cervix, uteri, kidney, lung, oesophagus, breast, colon, etc., contrasting with its restricted expression in normal tissues, namely in the epithelia of the gastrointestinal tract. It has been demonstrated that this membrane-bound CA is strongly overexpressed in hypoxic tumors, participating in tumor cell environment acidosis and contributing to malignant progression and poor treatment outcome. Targeting CA IX could thus be an important means of controlling cancer disease. Modulation of extracellular tumor pH via inhibition of CA IX activity represents a promising approach to novel anticancer therapies. Much attention has recently been paid to the CA IX inhibitors drug design, and efforts have been made to obtain isozyme IX inhibitors, with putative applications as antitumor drugs/diagnostic agents. This review will focus on the different CA IX inhibitors described in the literature which could represent excellent potential as candidate therapeutic agents in cancer chemotherapy.
Winum
Jean-Yves
JY
Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 Rue de l'Ecole Normale, 34296 Montpellier Cedex, France. winumj@univ-montp2.fr
Scozzafava
Andrea
A
Montero
Jean-Louis
JL
Supuran
Claudiu T
CT
D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002256:Carbonic Anhydrases / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases