Enhancement of Radiation Therapy Response in Prostate Cancer by Metabolic Modulation

Abstract

Motivation: When prostate cancer is treated with external beam radiation therapy (RT) with doses up to 78 Gy, gastrointestinal and genitourinary toxicities are often observed. Goal(s): Tumor sensitization by mito-lonidamine (mito-LND) will lower RT doses reducing the risk of adverse effects. Approach: The effects were assessed in vitro and in vivo in prostate cancer models using Seahorse, 1H and 31P MRS respectively. Results: Our findings showed a sustained and tumor-selective decrease in intracellular pH, bioenergetics, oxygen consumption rate and lactate. Selective tumor acidification, deenergization and oxygenation induced by mito-LND may improve the radiation response in prostate cancer. Impact: Exploiting the modulation of tumor metabolism and microenvironment for improving therapeutic efficacy of radiation therapy (RT) in early stage prostate cancer will lead to improved outcomes in prostate cancer patients.