The pHe of tumor tissues is often acidic [159] and this phenomenon is the result of multiple factors such as: (i) increased CO2 production, which is converted into carbonic acid by membrane Carbonic Anhydrases IX and XII (CAIX and CAXII) [160]; (ii) increased lactate production as a consequence of high glycolytic flux and aerobic glycolysis [161]; (iii) extrusion of this lactate by monocarboxylate transporters (MCTs) [162] and (iv) active translocation of cellular protons into the ECM mainly by sodium-hydrogen exchanger isoform-1 (NHE1) [163]. This evidence concerns the gene CA9 and neoplasm.