Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the reversible hydration of CO2 to bicarbonate and protons and are therefore involved in vital physiological processes. CA XII is a membrane isozyme that is upregulated in several tumor types. CA XII is crucial for the regulation of the intracellular pH and thus for the maintenance of cell function and survival. Additionally, the enzyme contributes to the acidification of the tumor microenvironment, which in turn promotes tumor invasion and migration.CA IX and CA XII contribute to the adaptation of malignant cells to hypoxia and acidosis through the regulation of intracellular and extracellular pH. High CA IX expression is found in the kidney, lung, colon, breast, cervix, ovary, brain, and few other tumors, while CA XII is overexpressed in the kidney, gastric, colorectal, breast, and brain tumors.