# A non-invasive blood test for multi-cancer detection and determination of tissue of origin preceding overt cancer diagnosis

> **NIH CA U01** · UNIVERSITY OF CHICAGO · 2026 · $676,491

## Abstract

PROJECT SUMMARY
In the United States, it is estimated there are ~730,000 new cases of prostate cancer, lung cancer, colorectal
cancer (CRC), and ovarian cancer annually. Advances in therapies during the past decades have significantly
improved clinical outcomes. For many common cancers, however, treatment options are limited when the
cancer is diagnosed with distant metastasis at later stages. Although early detection may reduce cancer
mortality, systematic screening programs are available only for a limited number of cancers (e.g., CRC), which
also faces challenges such as patient compliance and potential complications. Therefore, minimally-invasive
blood-based tools that could detect these common cancers at earlier stages are likely to be paradigm-shifting
in cancer control and care. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial offers
a unique opportunity and resource to investigate the possibility of applying our established 5hmC-Seal assay to:
1) explore cancer-specific early epigenetic marks, specifically 5-hydroxymethylcytosines (5hmC) in circulating
cell-free DNA (cfDNA), when the cancer is not “overt”; and 2) develop a multi-cancer detection (MCD) tool that
is minimally-invasive and possesses high sensitivity and specificity. Current MCD tests, e.g., Grail’s blood test,
are not suitable to exploit the PLCO samples (e.g., that contain very limited amounts of DNA). In contrast, the
5hmC-Seal assay, only requiring nanograms amounts of DNA, together with the next-generation sequencing
(NGS) holds the promise to address the challenge as a highly sensitive approach for PLCO biospecimens. Of
note, our compelling preliminary results demonstrated: 1) the feasibility of applying the 5hmC-Seal assay to
PLCO biospecimens (~200 µL plasma/sample); 2) analysis of genome-wide 5hmC from PLCO samples
successfully identified a 5hmC-based model that detected CRC cases months or even years prior to overt
disease; 3) altered 5hmC signatures associated 

## Key facts

- **NIH application ID:** 11324174
- **Project number:** 5U01CA297685-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Bruce Marc Bissonnette; Wei  Zhang
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $676,491
- **Award type:** 5
- **Project period:** 2025-05-01T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11324174

## Citation

> US National Institutes of Health, RePORTER application 11324174, A non-invasive blood test for multi-cancer detection and determination of tissue of origin preceding overt cancer diagnosis (5U01CA297685-02). Retrieved via AI Analytics 2026-07-14 from https://api.ai-analytics.org/grant/nih/11324174. Licensed CC0.

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