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Following treatment with LND, each of these tumors exhibits a rapid decrease in intracellular pH, a small decrease in extracellular pH, a concomitant monotonic decrease in nucleoside triphosphate and an increase in inorganic phosphate over a 2\u20133\u2009h period. We have previously demonstrated that selective intracellular tumor acidification potentiates response of this melanoma model to melphalan (7.5\u2009mg\/kg, i.v.), producing an estimated 89% cell kill based on tumor growth delay analysis. We now show that, in both DB\u20101 melanoma and HCC1806 breast carcinoma, LND potentiates response to doxorubicin, producing 95% cell kill in DB\u20101 melanoma at 7.5\u2009mg\/kg, i.v. doxorubicin and 98% cell kill at 10.0\u2009mg\/kg doxorubicin, and producing a 95% cell kill in HCC1806 breast carcinoma at 12.0\u2009mg\/kg doxorubicin. Potentiation of doxorubicin may result from cation trapping of the weakly basic anthracycline. Recent experience with the clinical treatment of melanoma and other forms of human cancer suggests that these diseases will probably not be cured by a single therapeutic procedure other than surgery. A multimodality therapeutic approach will be required. As a potent modulator of tumor response to N\u2010mustards and anthracyclines as well as tumor thermo\u2010 and radiosensitivity, LND promises to play an important clinical role in the management and possible complete local control of a number of prevalent forms of human cancer. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/nbm.3240","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T01:27:50Z","timestamp":1418347670000},"page":"281-290","source":"Crossref","is-referenced-by-count":74,"title":["Lonidamine induces intracellular tumor acidification and ATP depletion in breast, prostate and ovarian cancer xenografts and potentiates response to doxorubicin"],"prefix":"10.1002","volume":"28","author":[{"given":"Kavindra","family":"Nath","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Imaging, Department of Radiology, Perelman School of Medicine University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Imaging, Department of Radiology, Perelman School of Medicine University of Pennsylvania  Philadelphia PA 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