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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