Researchers developing improved exosome-based test for prostate cancer

Sanoj Punnen, M.D., co-chair of the Genitourinary Site Disease Group at Sylvester Comprehensive Cancer Center and associate professor and vice chair of research, Desai Sethi Urology Institute, at the University of Miami Miller School of Medicine, is leading a $2.5 million, five-year National Cancer Institute (NCI) grant to explore a new way to noninvasively detect prostate cancer.

(From left) Sannoj Punnen, M.D.; Sandra Gaston, Ph.D.; and Alan Pollack, M.D., Ph.D.

Biomarkers of significant prostate cancer that are detected in simple urine or blood tests are desperately needed to help reduce prostate biopsies — invasive, costly tests that are often negative and associated with potential complications, according to Dr. Punnen, the grant’s lead principal investigator (PI).

Prostate cancer screening saves lives but also results in unnecessary invasive prostate biopsies that are associated with overdiagnosis of low-grade cancers that do not need to be treated.

“There have been challenges and limitations in the past with detecting prostate cancer via urine and other noninvasive methods,” Dr. Punnen said. “But this proposal combines innovative technology from our collaborators at Exosome Diagnostics with well-annotated samples from an ongoing clinical trial of men undergoing biopsy for prostate cancer, placing us in an ideal position for developing a new platform of highly specific markers for prostate cancer detection. The NCI agreed.”

Dr. Punnen will work with co-PIs Alan Pollack, M.D., Ph.D., chair and professor of radiation oncology, and Sandra M. Gaston, Ph.D., assistant professor and director of the Molecular Biomarkers Analytic Laboratory in radiation oncology at Sylvester. The team will study small extracellular vesicles called exosomes as a promising new prostate cancer biomarker. Cancer cells release exosomes into body fluids, making it possible to extract them from blood and urine. These exosomes carry valuable molecular information from their parent tumors, including RNA and DNA, which the investigators hope to use to better estimate the risk of prostate cancer.

Improving Exosome-Based Test for Prostate Cancer

Desai Sethi and Sylvester researchers are collaborating with Exosome Diagnostics, a manufacturer in the field of exosome extraction and analyses that produces a commercially available exosome-based test for prostate cancer detection.

“Essentially, we’re taking their current marker and hope to make it better by developing it on a more prostate cancer-specific platform,” Dr. Punnen said.

Desai Sethi and Sylvester researchers are collaborating with Exosome Diagnostics, a manufacturer that produces a commercially available exosome-based test for prostate cancer detection

To do this, they will use information and specimens from an ongoing NCI-funded clinical trial (MDSelect, NCT04240327) of 250 men being evaluated for prostate cancer, in which researchers collect prostate biopsy tissue, blood and urine samples.

The hypothesis is that by selecting for exosomes that are tagged with a cell surface protein called “prostate specific membrane antigen” (PSMA), they will collect exosomes that are specifically secreted from prostate cancer cells, which would provide more accurate prostate cancer risk evaluation. Dr. Punnen and colleagues will test the hypothesis in the ongoing MDSelect trial he is leading. The goal is to develop and validate a novel, non-invasive, exosome-based signature to enhance the accuracy of detecting clinically significant prostate cancer.

This project is multidisciplinary — an excellent example of team science, according to Dr. Gaston.

“Molecular biologists are involved in biomarker discovery and test development. Clinicians take the lead in defining the most appropriate applications for the new tests and help develop the study design to validate them. Pathology, bioinformatics and MR imaging specialists play important roles providing supporting data to contribute to marker validation,” Dr. Gaston said. “In addition to the senior M.D. and Ph.D. investigators, our project relies on an experienced team of technicians and study coordinators who ensure that the work moves forward as a smooth, well-organized operation.”

The momentum behind the latest grant is the result of a decade of research at the Miller School, according to Dr. Pollack.

“If this platform is validated, it will have important implications for patients by helping to reduce the need for invasive biopsies. The noninvasive testing might also be used as a marker of prostate cancer treatment response and/or progression,” Dr. Pollack said.

This research aims to reduce the burdens of prostate cancer screening by substantially enhancing prostate cancer risk evaluation and reducing unnecessary and invasive prostate biopsies to improve the quality of life of men undergoing prostate cancer evaluation.

SourceUniversity of Miami Miller School of Medicine

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