Recent Developments in Targeting Carbonic Anhydrase IX for Cancer Therapeutics

Abstract

Paul C. McDonald 1 , Jean-Yves Winum 2 , Claudiu T. Supuran 3 and Shoukat Dedhar 1,4 1 Department of Integrative Oncology, BC Cancer Research Centre and BC Cancer Agency, Vancouver, BC, Canada 2 Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, EcoleNationale Supérieure de Chimie de Montpellier, 8 rue de l’Ecole Normale, 34296 Montpellier Cedex, France 3 Laboritario di Chimica Bioinorganica, Universita degli Studi di Firenze, Italy 4 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada Received: January 4, 2012; Accepted: January 4, 2012; Published: January 28, 2012; Keywords: cancer, hypoxia, carbonic anhydrase IX, metastasis, targeted therapeutics Correspondence: Shoukat Dedhar, email: // // Abstract Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor cell growth and survival, while at the same time participating in the generation of an increasingly acidic extracellular space, facilitating tumor cell invasiveness. Pharmacologic interference of CAIX catalytic activity using monoclonal antibodies or CAIX-specific small molecule inhibitors, consequently disrupting pH regulation by cancer cells, has been shown recently to impair primary tumor growth and metastasis. Many of these agents are in preclinical or clinical development and constitute a novel, targeted strategy of cancer therapy.