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Its expression is strongly induced by hypoxia present in many tumors, being regulated by the HIF transcription factor and correlated with a poor response to classical chemo\u2010 and radiotherapies. CA IX was recently shown to contribute to acidification of the tumor environment, by efficiently catalyzing the hydration of carbon dioxide to bicarbonate and protons with its extracellularly situated active site, leading both to the acquisition of metastasic phenotypes and to chemoresistance with weakly basic anticancer drugs. Inhibition of this enzymatic activity by specific and potent inhibitors was shown to revert these acidification processes, establishing a clear\u2010cut role of CA IX in tumorigenesis. The development of a wide range of potent and selective CA IX inhibitors belonging to diverse chemical classes, such as membrane\u2010impermeant, fluorescent or metal\u2010containing such agents, could thus provide useful tools for highlighting the exact role of CA IX in hypoxic cancers, to control the pH (im)balance of tumor cells, and to develop novel diagnostic or therapeutic applications for the management of tumors. Indeed, both fluorescent inhibitors or positively charged, membrane impermeant sulfonamides have been recently developed as potent CA IX inhibitors and used as proof\u2010of\u2010concept tools for demonstrating that CA IX constitutes a novel and interesting target for the anticancer drug development. \u00a9 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 3, 445\u2013463, 2008<\/jats:p>","DOI":"10.1002\/med.20112","type":"journal-article","created":{"date-parts":[[2007,9,19]],"date-time":"2007-09-19T19:47:56Z","timestamp":1190231276000},"page":"445-463","source":"Crossref","is-referenced-by-count":225,"title":["Carbonic anhydrase IX: A new druggable target for the design of antitumor 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