title: Targeting carbonic anhydrase IX activity and expression.
abstract: Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer.
authors: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA.
authors: Brian P
authors: BP
authors: Mahon
authors: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA.
authors: Melissa A
authors: MA
authors: Pinard
authors: Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA. rmckenna@ufl.edu.
authors: Robert
authors: R
authors: McKenna
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000201:enzymology / Q000628:therapy*; D040681:Structural Homology, Protein
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
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