Use of the Proton Pump Inhibitor Pantoprazole to Modify the Distribution and Activity of Doxorubicin: A Potential Strategy to Improve the Therapy of Solid Tumors

PURPOSE: Limited drug distribution within solid tumors is an important cause of drug resistance. Basic drugs (e.g., doxorubicin) may be sequestered in acidic organelles, thereby limiting drug distribution to distal cells and diverting drugs from their target DNA. Here we investigate the effects of pantoprazole, a proton pump inhibitor, on doxorubicin uptake, and doxorubicin distribution and activity using in vitro and murine models.