# Clinical Translation of a Large Oncosome-Based Prostate Cancer Blood Test

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2024 · $649,486

## Abstract

ABSTRACT - The focus of this proposal is on lethal, metastatic prostate cancer (PC). The aim of this study
is to develop an innovative, minimally invasive, liquid biopsy assay that can be used to identify molecular
subtypes of lethal prostate cancer PC in patients with a biologically aggressive disease. Phenotyping Large
Oncosomes for Ultimate Evaluation of Patients Status (PLUS) will identify biomarkers of short/long response to
treatment, and progressively assess tumor phenotype during PC evolution and under treatment pressure. We
propose to focus on extracellular vesicles (EV) known as large oncosomes (LO) that are identified in the plasma
of patients with aggressive cancer. Using gold standard methods, we obtained pure populations of LO and
performed extensive mass spectrometry and NGS experiments that identified a set of proteins and RNA markers
that have been validated by multiple experiments in vitro and in a few pilot patient cohorts, as explained in
preliminary results. In this application, we will employ innovative technologies to translate our efforts to define
LO-based signatures to the CLIA laboratory to determine clinical utility of our liquid biopsy approach in PC
patients with lethal disease, both in the castration resistant and hormone sensitive space. We will leverage an
expansive cohort of clinically annotated PC specimens (N=600), both retrospectively and prospectively collected
from 2 independent sites. In Aim 1, we will perform analytical validation of LO isolation technologies for clinical
use. In Aim 2, we will develop an LO-centered multianalyte assay to detect lethal PC and predict ARSI response.
In Aim 3 we will assess the sensitivity and specificity of PLUS in metastatic hormone-sensitive PC patients to
predict lethal outcomes. We will continue to focus on PC because of the significance of PC open clinical
questions, of the challenges relative to this tumor-type in liquid biopsy development, and our extensive
experience in the field of PC molecular landscape. Yet, there is great opportunity for our LO-based assay to be
expanded to other tumor types in the future. Our study is technologically innovative and will likely result in the
identification of new markers and ultimately in the application of a microfluidic device to the CLIA lab. The M-PI
team brings expertise not only on EVs (Di Vizio, Stott, Demichelis), but also on ctDNA (Demichelis) and CTCs
(Stott) and propose orthogonal approaches to determine which method, among bead-based and microfluidic
capture, which will be benchmarked against density gradients, has the best performance in a complex clinical
lab.

## Key facts

- **NIH application ID:** 10990336
- **Project number:** 1R01CA287075-01A1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Francesca Demichelis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $649,486
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990336

## Citation

> US National Institutes of Health, RePORTER application 10990336, Clinical Translation of a Large Oncosome-Based Prostate Cancer Blood Test (1R01CA287075-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10990336. Licensed CC0.

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