Carbonic anhydrase IX as a marker of hypoxia in gliomas: A narrative review

Abstract

Hypoxia is a powerful driver of the malignant phenotype in solid tumors including gliomas. A major, though not sole, driver of this effect is the hypoxia-inducible factors (HIF) which promote the expression of hundreds of downstream genes through binding with hypoxia-responsive elements in the promoter regions of targeted genes. HIF-2α drives the cancer stem cell phenotype that has been shown to promote chemo- and radioresistance. HIF-1α drives the transcription of a number of genes, the most prolific and important of which appears to be that of CAIX, but also drives the transcription of VEGF and a number of glycolytic enzymes, thus participating in driving the Warburg effect. This brief review introduces how the localization of CAIX by immunohistochemistry has, though still in its early phases, allowed the identification of gliomas with worse prognosis, an application of significant importance in diagnostic neuropathology. The future of hypoxia research will manipulate these downstream pathways to provide further biomarkers through which the presence of hypoxia and its effects can be established, analyzed, and exploited.