# Integrative Functional Profiling of Tumor-Derived Extracellular Vesicles

> **NIH NIH R33** · UNIVERSITY OF FLORIDA · 2023 · $64,488

## Abstract

PROJECT SUMMARY
Clinical implementation of Precision Medicine faces major challenges in precision disease stratification and
staging, determining optimal treatment, monitoring therapy response, and overcoming drug resistance and
relapse. To address these challenges, there is a critical unmet need for better biomarkers and tests that
complement current methods for accurate diagnosis, prognosis and monitoring of response to treatments. Liquid
biopsy presents an innovative non-invasive modality for precision oncology as it promises to provide a global
view of tumor dynamics. Extracellular vesicles (EVs), including exosomes, are emerging as a new paradigm of
liquid biopsy for non-invasive cancer diagnosis and monitoring. Exosomes are 40-150 nm membrane vesicles
secreted by most cells and have been identified as essential mediators of cell interactions and signaling that
promote tumor metastasis, drug resistance, and relapse. Despite the potential clinical impact of these findings,
precise biological functions of exosomes, including matrix metalloproteinases (MMPs)-mediated modulation of
tumor microenvironments, and their potential clinical value remain yet to be determined. This is due in part to
the daunting challenges in isolation and analysis of these nanovesicles with diverse molecular and functional
properties. Here we hypothesize that functional phenotypes of circulating exosomes can provide potent
biomarkers for detecting early malignancy, monitoring tumor progression and metastasis, and assessing therapy
response in breast cancer. To test this hypothesis, we propose the advanced development and validation of a
nano-engineered microfluidic biosensing system capable of integrative analysis of both molecular and functional
phenotypes of exosomes in one streamlined workflow. The research will be performed by three specific aims: 1)
Expand the MINDS strategy to develop an optimal 3D nano-engineered integrative EV molecular and activity
profiling (EV-MAP) nanochip platform; 2) Adapt and optimize the EV-MAP technology for monitoring tumor
burden and therapy response using mouse models; and 3) Evaluate and validate the EV-MAP technology for
potential applications to clinical diagnosis and classification of breast cancer patients. The new technology will
confer superior analytical capabilities to substantially accelerate the functional studies of circulating exosomes.
Harnessing exosome activities for diagnostic, prognostic or therapeutic benefit presents a paradigm-shifting
mechanism for precision medicine. While focused on breast cancer in this project, our research will ultimately
create a transformative tool for studies of a wide range of bioactive exosomes in various malignancies to develop
reliable non-invasive liquid biopsy of cancer.

## Key facts

- **NIH application ID:** 10679069
- **Project number:** 5R33CA252158-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Liang Xu
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $64,488
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679069

## Citation

> US National Institutes of Health, RePORTER application 10679069, Integrative Functional Profiling of Tumor-Derived Extracellular Vesicles (5R33CA252158-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10679069. Licensed CC0.

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