Study Highlights Potential of Mito-LND to Improve Prostate Cancer Treatment
Balaraman Kalyanaraman, PhD, in the Department of Biophysics collaborated with scientists nationally and internationally on a strategy to optimize radiation therapy in prostate cancer. The study, titled “Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A 1H and 31P Magnetic Resonance Spectroscopy Study” and published in International Journal of Molecular Sciences, highlights the potential of mitochondria-targeted lonidamine (LND) to improve prostate cancer treatment.
Prostate cancer is the second most common cancer in men worldwide, and a leading cause of cancer death globally. Early-stage prostate cancer is treated primarily through surgery and/or radiation therapy. Although radiation therapy has a critical role in the treatment of prostate cancer, it frequently damages surrounding healthy tissues. In the present work, the authors studied the metabolic effects of LND and Mito-LND, a modified version of lonidamine designed to target mitochondria, in prostate cancer models. The authors found that Mito-LND had a more substantial radiosensitizer effect than LND in the models, as well as the ability to alter the tumor microenvironment and interfere with androgen receptor signaling; together, these strengthen the potential of Mito-LND to enhance the efficacy of radiotherapy in prostate cancer treatment.
Mito-LND represents a novel strategy to decrease tumor hypoxia via selective inhibition of mitochondrial respiration and to enhance the response to radiotherapy, which could enable more effective treatment of patients with early-stage prostate cancer as well as reduce the adverse effects of high doses of radiotherapy. Ultimately, the use of Mito-LND in combination with radiotherapy could improve patient outcomes and reduce morbidity.
Additional authors of the study include Stepan Orlovskiy, Pradeep Kumar Gupta, Fernando Arias-Mendoza, Dinesh Kumar Singh, Skyler Nova, David S. Nelson, Vivek Narayan, Cameron J. Koch, and Kavindra Nath (corresponding author) at the University of Pennsylvania; Micael Hardy at Aix-Marseille University, and Ming You at Houston Methodist Research Institute.