Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: Three for the price of one

Med Res Rev. 2018 Sep;38(6):1799-1836. doi: 10.1002/med.21497. Epub 2018 Apr 10.


Human carbonic anhydrase (CA) IX is a tumor-associated protein, since it is scarcely present in normal tissues, but highly overexpressed in a large number of solid tumors, where it actively contributes to survival and metastatic spread of tumor cells. Due to these features, the characterization of its biochemical, structural, and functional features for drug design purposes has been extensively carried out, with consequent development of several highly selective small molecule inhibitors and monoclonal antibodies to be used for different purposes. Aim of this review is to provide a comprehensive state-of-the-art of studies performed on this enzyme, regarding structural, functional, and biomedical aspects, as well as the development of molecules with diagnostic and therapeutic applications for cancer treatment. A brief description of additional pharmacologic applications for CA IX inhibition in other diseases, such as arthritis and ischemia, is also provided.

Keywords: antibodies; carbonic anhydrase IX; diagnostic tools; drugs; hypoxic tumors; small molecule inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Carbonic Anhydrase IX / chemistry
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis / drug therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*


  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase IX