# Longitudinal therapeutic monitoring of colorectal cancer patients using exosome-based liquid biopsies

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $663,998

## Abstract

Project Summary and Relevance:
Exosomes are bi-layered lipid microvesicles containing DNA, RNA and proteins, which have emerged as an
important avenue for cell-cell communication in cancer. Our team has performed pioneering studies on the utility
of circulating exosomes for genomic and transcriptomic profiling of visceral cancers that are challenging to
sample longitudinally. Specifically, we have demonstrated the remarkable integrity of the nucleic acid cargo
(exoDNA and exoRNA) contained within exosomes, which makes them readily amenable to next generation
sequencing (NGS). The objective of this proposal is to establish the utility of liquid biopsies that enrich for high
quality exosomes as a platform for therapeutic stratification and disease monitoring in advanced colorectal
cancer (CRC). In Aim 1 will meticulously evaluate the most appropriate methodology for reproducible and
sensitive isolation of circulating exosomes from metastatic CRC patients using gradient ultracentrifugation versus
two of the most commonly used commercial kits. We will develop perform rigorous biological and technical
reproducibility assays on the isolated exosomes and nucleic acid cargo that will develop standards necessary
for translation of exosomal-based “liquid biopsy” to a clinical molecular diagnostics laboratory (MDL). We will
also perform mass spectrometry-based proteomic profiling of exosomes isolated from a panel of CRC organoid
models versus control organoids and cell lines, in order to identify the surface proteins (“surfaceome”) present
on CRC-derived exosomes. The surfaceome data will serve as an invaluable tool for enrichment of cancer-
specific exosomes in low-volume tumor settings, such as minimal residual disease monitoring. In Aim 2, we will
compare targeted mutation panel and copy number profiles of tissue samples in patients undergoing surgical
debulking for metastatic (m)CRC, with that of corresponding plasma exoDNA-derived profiles. The remarkable
preservation of exoRNA within exosomes will allow us to perform RNA-Seq and compare the consensus
molecular subtype (CMS) classification obtained by shed exosomes versus metastatic tissues. Finally, in Aim
3, we will longitudinally monitor cohorts of surgically resected CRC patients, or mCRC patients on two
prospective clinical trials, using exosomes as a molecular tool for identifying disease recurrence and emergence
of treatment resistance, respectively. The first trial will evaluate for emergence of low frequency KRAS mutations
and other secondary drivers of resistance to EGFR-based therapies. The second trial is an immunotherapy trial
of multivalent peptide vaccine, where exoRNA data will also be used to predict, and then monitor, expressed
neoantigens in mCRC samples, using bioinformatics tools we have developed for mapping transcript data to
HLA-presented peptides on the cancer cell surface. The long-term goal of these studies is to generate the
compendium of standards and assays needed for succ...

## Key facts

- **NIH application ID:** 9959362
- **Project number:** 5R01CA218230-03
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Scott Kopetz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $663,998
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959362

## Citation

> US National Institutes of Health, RePORTER application 9959362, Longitudinal therapeutic monitoring of colorectal cancer patients using exosome-based liquid biopsies (5R01CA218230-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9959362. Licensed CC0.

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