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Abstract #0128

Metabolic modulation towards improved outcome in human glioblastoma model

Kavindra Nath1, David Nelson1, Jeffrey Roman1, Sofya Osharovich1, Saad Sheikh2, Stepan Orlovskiy1, Stephen Pickup1, Dennis Leeper3, Yancey Gillespie4, Corrine Griguer5, Jay Dorsey2, Mary Putt6, and Jerry Glickson1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States, 3Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States, 4Neurosurgery, University of Alabama, Birmingham, AL, United States, 5Radiation Oncology, University of Iowa, Iowa City, IA, United States, 6Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States

Standard of care for glioblastoma multiforme (GBM) patients, the Stupp protocol, involves radiotherapy concurrent with adjuvant temozolomide (TMZ) chemotherapy. Lonidamine (LND), an inhibitor of monocarboxylate transporters, mitochondrial pyruvate carrier and mitochondrial complex I & II, is shown to potentiate TMZ chemotherapy inhibiting the growth of U251 glioblastoma cells orthotopically implanted in mice. LND effects measured in vivo by 31P and 1H MRS in subcutaneous U251 glioblastoma xenografts showed a sustained and tumor-selective decrease in intracellular pH, decrease in bioenergetics (╬▓NTP/Pi) and an increase in lactate. Selective tumor acidification and deenergization induced by LND potentiated the TMZ response in U251 glioblastoma xenografts.

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