CTSB and adrenal cortex carcinoma: Thus, ACC’s therapeutic effect is most likely attributed to the cumulative effects caused by elevating the pHe in the TME, such as the following: (a) lower metastases [7,8,9,10,16,31,32,33,68,69,70]; (b) lower proliferation rates [7,10,14,71]; (c) reduced cathepsin B and other protease activities [15]; (d) increased immune-system ability to react in the tumor environment [21,72]; and (e) decreased chemoresistance [73,74].