While most of the work on carbonic anhydrases in cancer has focused on CAIX as a biomarker, studies from several groups have highlighted the importance of the carbonic buffer system for pH regulation in various cancer cell lines under normal, acidic, and hypoxic growth conditions When cancer cell lines from pancreas, breast, and colon were grown in 2D culture, the mechanism of net acid extrusion after an imposed acid load varied between cell lines, from mainly HCO−3 influx to mainly H+ efflux (Hulikova et al., 2011). The gene discussed is CA9; the disease is cancer.