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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Antibodies, Monoclonal / therapeutic use
-
Antigens, Neoplasm* / chemistry
-
Antigens, Neoplasm* / genetics
-
Antigens, Neoplasm* / immunology
-
Antigens, Neoplasm* / physiology
-
Antineoplastic Agents / administration & dosage
-
Antineoplastic Agents / therapeutic use*
-
Carbonic Anhydrase IX
-
Carbonic Anhydrases* / chemistry
-
Carbonic Anhydrases* / genetics
-
Carbonic Anhydrases* / immunology
-
Carbonic Anhydrases* / physiology
-
Gene Expression Regulation, Enzymologic / physiology
-
Gene Expression Regulation, Neoplastic / physiology
-
Humans
-
Medical Oncology / methods
-
Medical Oncology / trends*
-
Molecular Targeted Therapy / methods*
-
Molecular Targeted Therapy / trends
-
Neoplasms / drug therapy*
-
Neoplasms / genetics
-
Neoplasms / pathology
-
Protein Conformation
Substances
-
Antibodies, Monoclonal
-
Antigens, Neoplasm
-
Antineoplastic Agents
-
CA9 protein, human
-
Carbonic Anhydrase IX
-
Carbonic Anhydrases