ABSTRACT
Insufficient tissue perfusion in malignancies results in hypoxic areas, favoring neoplastic progression. Tumor cells under hypoxia undergo an adaptive program by activating alternative metabolic pathways, which is regulated by hypoxia inducible factor-1 (HIF1) in order to overcome microenvironmental changes. The expression of carbonic anhydrase IX (CAIX) is a prominent protective mechanism against intracellular acidosis occurring in cancer cells suffering from hypoxia. Due to the activity of CAIX, the restored intracellular pH (pHi) supports tumor cell proliferation and migration, while the compensatory extracellular acidosis contributes to immunoprotection and to chemo- and radioresistance. In vitro and animal model experiments showed that the chemotherapeutic efficiency could be significantly improved by the selective inhibition of CAIX, thus, its adjuvant therapeutic potential is under active investigation.
