CA9 and neoplasm: Acidosis is another environmental stress caused by the accumulation of tumor-derived acid, such as lactate, H+, and CO2; increased H+ efflux via membrane-associated H+ transporters, such as H+-ATPase, Na+-H+ exchanger, and HCO3− exchanger, in association with enhanced extracellular hydration of CO2 by membrane-bound carbonic anhydrase 9; and reduced elimination of tumor-derived acid due to poor perfusion [3].