Exosomal RNA: A Novel Signature Guide for Prostate Cancer Proton Therapy

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Project Summary / Abstract Proton therapy (PT) is a form of radiation therapy used to treat prostate cancer patients that can be an alternative to surgery. While PT is thought to risk less toxicity than conventional radiation therapy, much about PT is still not understood. To help serve their local area of tidewater Virginia, which has one of the highest rates of prostate cancer in the world, especially in African-Americans, Hampton University (HU), a Historically Black University, has opened the Hampton University Proton Therapy Institute. To help build the research capacity at HU, leveraging their clinical expertise in proton therapy, the Icahn School of Medicine at Mount Sinai (ISMMS) and HU propose this joint project aimed at developing a noninvasive biomarker for response to PT. The team at ISMMS will bring their expertise in genomics and exosome profiling, a noninvasive way to measure particles that are thought to shed from the tumor, to this project and in the process help build the research capacity at HU. The research goal of this project is to determine changes in the exosomal RNA (exoRNA) profile of exosomes taken from prostate cancer patients before and after radiotherapy with PT. All aims of the study use patient samples collected at the HUPTI by the HU team. In aim 1, we will ask if an exosomal signature of radical prostatectomy shows similar changes before and after PT. In aim 2, to determine if there are specific changes in the mRNA profile in response to PT, we will globally profile RNA isolated from exosomes before and after PT. In aim 3, to continue to build this project in preparation for a future collaborative R01 submission, we will recruit additional patients from HUPTI to this study and obtain blood specimens before, during, and after PT. At the end of the study time period, our scientific achievement will have been to determine what changes in the RNA profile of exosomes can be observed in response to PT. This will be important preliminary data demonstrating the utility of exosomes for noninvasive monitoring of PT. More importantly, through this collaborative partnership between ISMMS and HU, we will have enhanced the research infrastructure of HU in a way that will allow HU to pursue further research both jointly with ISMMS and independently building on their clinical expertise in proton therapy.