Manipulating extracellular tumour pH: an effective target for cancer therapy

The pH in tumour cells and the tumour microenvironment has played important roles in cancer development and treatment. It was thought that both the extracellular and intracellular pH values in tumours are acidic and lower than in normal cells. However, recent progress in the measurement of pH in tumour tissue has disclosed that the intracellular pH (pH(i)) of cancer cells is neutral or even mildly alkaline compared to normal tissue cells. This review article has summarized the recent advancement in the measurement pH(i) and extracellular pH (pH(e)) in cancer cells, and the effect of pH(i) and pH(e) on proliferation, migration and biological functions of cancer cells. This paper has also elaborated recent treatment strategies to manipulate pH(i) and pH(e) for cancer treatment. Based on the recent progress in pH(i) and pH(e) manipulation in cancer treatment, we have proposed potential nanoparticle-based strategies to manipulate pH(i) and pH(e) to effectively treat cancer.