Proton pump inhibitors and other pH-buffering agents

By a metabolism based on sugar fermentation, cancer cells progressively acidify their microenvironment inducing a selective pressure which leads to the development of very malignant cells entirely armed to survive in such a hostile microenvironment. Proton exchangers, among which vacuolar ATPases (V-ATPases), do not permit the intracellular acidification by a constant elimination of H+ either outside the cells or within the internal vacuoles. This chapter describes the translational process that provided the preclinical to clinical demonstration of the potentiality of proton pump inhibitors (PPIs), exploited worldwide for peptic ulcer treatment and gastroprotection, as chemosensitizers or even antitumor agents as well.