This notion is supported by reports of reduction in the incidence of metastases in breast cancer models by CAIX inhibition40–42 and in a prostate cancer model by CAIX silencing.43 Thus, the pH-stat function of CAIX is likely to extend to the growing margin of the solid tumour, distant from optimal oxygen supplies, allowing leading-edge cells to set tissue pHe at a level inhibitory to normal tissue and thus facilitating invasion of cancer cells. The gene discussed is CA9; the disease is breast carcinoma.