CA9 and cancer: Key pH regulatory components that cancer cells upregulate in hypoxia include membrane-bound, extracellular carbonic anhydrases (CAs), particularly CAIX and CAXII, which maintain an intracellular and extracellular acid-base balance (McDonald et al., 2012; Damaghi et al., 2013; McDonald and Dedhar, 2014), and monocarboxylate transporters (MCTs), especially MCT4, which facilitate lactate extrusion (Marchiq and Pouysségur, 2015).