On the other hand, based on a more comprehensive and clear regulatory network of CAXIIis, more chances could be gained by expanding their application in different combination therapies with multiple targets for treating cancer, as shown in a preclinical study that combined CAIX and CAXII dual inhibition with immune checkpoint blockade resulting in improved efficacy of immune therapy in melanoma and breast cancer (53). The gene discussed is CA9; the disease is breast carcinoma.