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Abstract #3800

Lonidamine-induced selective acidification and deenergization of prostate cancer xenografts: Enhanced tumor response to radiation therapy

Kavindra Nath1, Jeffrey Roman1, David Nelson1, Mary Putt1, Stepan Orlovskiy1, Ewere Azagidi1, Violet Tu1, Dennis Leeper2, and Jerry Glickson1

1University of Pennsylvania, Philadelphia, PA, United States, 2Thomas Jefferson University, Philadelphia, PA, United States

Prostate cancer, when treated with external beam radiotherapy (RT) in the range of 78 Gy, is frequently associated with gastrointestinal (GI) & genitourinary (GU) toxicities. We hypothesize that tumor sensitization by lonidamine (LND) will enable the use of lower RT doses reducing the risk of side effects. LND effects detected in vivo by 31P and 1H MRS in androgen-independent (PC3) prostate cancer xenografts produced a sustained and tumor-selective decrease in intracellular pH, bioenergetics (βNTP/Pi), oxygen consumption rate and increase in lactate. Selective tumor acidification, deenergization and oxygenation induced by LND potentiated the radiation response in the PC3 prostate cancer model.

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