Abstract：
:Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environment by efficiently catalyzing the hydration of carbon dioxide to bicarbonate and protons, thereby leading to acquisition of metastatic phenotypes and chemoresistance to weakly basic anticancer drugs. Inhibition of this enzymatic activity by specific inhibitors, such as the sulfonamide indisulam, reverts these processes, establishing a clear-cut role for CA IX in tumorigenesis. Thus, selective CA IX inhibitors could prove useful for elucidating the role of CA IX in hypoxic cancers, for controlling the pH imbalance in tumor cells and for developing diagnostic or therapeutic applications for tumor management. Indeed, fluorescent inhibitors and membrane-impermeant sulfonamides have recently been used as proof-of-concept tools, demonstrating that CA IX is an interesting target for anticancer drug development.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Thiry A,Dogné JM,Masereel B,Supuran CTdoi
10.1016/j.tips.2006.09.002subject
Has Abstractpub_date
2006-11-01 00:00:00pages
566-73issue
11eissn
0165-6147issn
1873-3735pii
S0165-6147(06)00220-3journal_volume
27pub_type
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