Carbonic Anhydrases constitute a family of structurally divergent proton exchange proteins and particularly CA9 and CA12 have been previously described in GBM and other tumor entities as tumor cell-intrinsic carbonic anhydrases [17,18] and a current clinical trial uses acetazolamide in conjunction with TMZ (trial number NCT03011671) in GBM patients. This evidence concerns the gene CA12 and glioblastoma.