Carbonic anhydrase IX as a target for metastatic disease

Bioorg Med Chem. 2013 Mar 15;21(6):1470-6. doi: 10.1016/j.bmc.2012.09.062. Epub 2012 Oct 11.

Abstract

Metastatic disease is responsible for the majority of cancer related deaths. Tumour-associated carbonic anhydrase IX (CA IX) is a powerful marker to diagnose various types of metastatic cancers including those of cervical, renal, breast and head & neck origin. The precise prognostic role of CA IX in determining local control versus overall survival is complex, although the majority of reports favour CA IX as a marker for poor prognosis in patients with metastatic cancer. Preclinical studies in cell cultures clearly demonstrate that CA IX stimulates features that enhance metastatic properties of cancer cells for example, reducing cell adhesion, increasing motility and migration, inducing vascularisation and activating proteases, in which CA IX-induced acidification of the microenvironment of the tumour is essential. As most findings are consistent with the idea that CA IX is important in metastatic dissemination, small molecular CA IX inhibitors (including fluorescent-tagged or radiolabelled) and monoclonal antibodies targeting the CA IX isoform have been developed. Studies in tumour xenograft models showed that these CA IX-specific inhibitors and antibodies can be very effective in therapy and imaging of a variety of different metastatic cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / therapeutic use
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Female
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / pathology
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / pathology
  • Lymphatic Metastasis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / therapeutic use
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Small Molecule Libraries
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases