title: Designing carbonic anhydrase inhibitors for the treatment of breast cancer.
abstract: BACKGROUND
  Carbonic anhydrase (CA) IX is one of the proteins that are involved in cancerogenesis in hypoxic breast tumors. Indeed, it is present in high amounts in hypoxic tumor cells, where it plays a crucial role in metabolic reprogramming due to the scarcity of oxygen, triggered by the hypoxia inducible factor 1 transcription factor. In such tumors, CA IX is involved, along with other proteins, in tumor pH regulation and its survival in a harsh environment (including hypoxia and acidity). CA IX is also validated as an imaging and treatment target for hypoxic tumors and metastasis.
  
  
  METHODS
  In this review, the authors highlight the wealth of CA IX inhibitors currently in the literature. This includes the two most investigated classes of compounds being the sulfonamides and the coumarins, including their isosteres.
  
  
  CONCLUSIONS
  The most advanced CA IX inhibitors candidates, which demonstrate antimetastatic activity in breast cancer, are the sulfonamides, with one compound (SLC-0111) currently in Phase I clinical development. The fact that this first inhibitor has progressed could increase interest in the development of conceptually novel antitumor/antimetastic drugs belonging to the CA inhibitors class.
authors.affiliation: UniversitàdegliStudi di Firenze, Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences , Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence , Italy claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects; D015687:Cell Hypoxia; D015195:Drug Design; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: breast tumors; carbonic anhydrase; coumarins; hypoxia; inhibitors; isoform hCA IX; sulfonamides