New Anti-cancer Strategies to Reverse the Abnormal pH Gradient of Tumor Microenvironment

External acidification and internal alkalization are common in different types of malignant tumors. The formation of this abnormal microenvironment of pH gradient is closely related to the tissue structure and metabolic characteristics of tumor cells. The maintenance of the negative pH gradient in the microenvironment is closely related to some ion exchange proteins such as Na⁺/H⁺ exchanger-1 (NHE-1), vacuolar proton pump (V-ATPase), HCO₃^- transporter and so on. Carbonic anhydrase (CA) also plays an important role for the maintenance of the pH gradient in the microenvironment. This article reviews the causes of abnormal pH of tumor and the influence on its growth and progression, and some treatment strategies to reverse the abnormal pH gradient of tumor microenvironment, so as to provide some ideas for the development of related drugs.