To prevent the toxic intracellular acidification, tumor cells trigger the expression of proton extrusion mechanisms, including proton flux regulators, such as vacuolar H+-ATPases, Na+/H+ exchanger, monocarboxylate transporters, carbonic anhydrase IX and Na+/HCO3 co-transporters (reviewed in [48,49,50,51]). The gene discussed is CA9; the disease is neoplasm.