Proton pump inhibitors as chemosensitizer: New indication for a well-known medication

In the last decades, resistance to chemotherapy has become a major problem in the treatment of different tumors, resulting in unfavorable therapeutic success and worse patient survival. Among other mechanisms of multidrug resistance, in-vitro studies demonstrated that tumors present changes in microenvironment that lead to pH alterations, and acidic tumor microenvironment modulates sensitivity to chemotherapy, cancer progression and metastasis in cancer cell lines. Currently, various potential therapeutic strategies targeting intracellular pH regulation and metabolic interactions in tumor cells are under investigation. Proton pump inhibitors (PPIs) are one of the most promising therapeutic approaches in this context - due in particular to their worldwide clinical use, good availability and low side effect profile. PPIs influence pH balance, and recent studies have shown increased chemosensitivity of tumor cells and enhanced cytotoxicity of chemotherapeutic drugs after treatment with PPIs. This brief review discusses the use of PPIs as chemosensitizer in tumors in-vitro and in-vivo on the basis of the current literature.