The pH-centered paradigm in cancer

We have not yet found the silver bullet that can kill cancer cells without seriously affecting normal cells. However, there is one constant feature of cancer that is not usually present in normal tissues: an inverted pH gradient, where the intracellular pH becomes alkaline and the extracellular pH becomes acidic. This has been called the cancer pH-centered paradigm. This alteration, which has not yet received adequate consideration in cancer therapeutics—is a hallmark of all malignant cells and tissues. Research in the last 20 years has shown that modifying this abnormal pH has profound effects on the development of cancer and that pharmacological interventions are not only feasible but also have little effects on normal tissues. Strong evidence indicates that most of the pharmacological interventions that modify the pH gradient are compatible with standard treatments and enhance their results. This chapter will analyze the mechanisms involved in the pH inversion and its clinical implications.