Exosomal RNAs as Serum Prostate Cancer Biomarkers—Personalized Treatment and Better Prognostic Indicators May Become Reality Through MicroRNA Tumor Profiling

Investigator: Muneesh Tewari, MD, PhD–Assistant Member, Fred Hutchinson Cancer Research Center, University of Washington

MicroRNAs, small RNA molecules that regulate gene expression, have been found to circulate in blood within lipid membrane-encased particles (exosomes) that are secreted from and blebbed off of cancer cells. These molecules which are “spit” into the blood stream appear cancer-specific and hold great promise for molecular profiling of tumors. This project is on the cutting edge of a new technology whereby diagnosis, prognosis and optimal treatment strategy might be determined by analysis of circulating microRNAs. Dr. Tewari will optimize the isolation of exosomes and purification of microRNAs from prostate cancer models followed by genetic probing of these materials. This technology may ultimately be useful to patients for personalized treatment and improved prognostic information and is utterly original.

Progress Report:

Dr. Tewari and colleagues have discovered that cancer cells shed tiny vesicles from their membrane, much like humans shed hair or dead skin. These vesicles, termed exosomes, package a sampling of the molecular milieu found within the cancer cell and can be captured in blood. Enveloped within the exosomes are molecules that carry important information about the cancer called microRNAs and mRNAs. Identifying and quantifying these molecules real time in a patient has the potential of guiding therapy decisions. Dr. Tewari’s project goal was to optimize the technology for isolating exosomes and extracting their content to define the molecular profile a patient’s prostate cancer. The team has developed a novel method of physically stimulating the release of exosomes from prostate cancer cells. They are currently testing and validating this new technology in mouse models before proceeding to studies with patient specimens.