# DNA evaluation of fragments for early interception (DELFI) of Lung cancer

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $1,001,112

## Abstract

Project Summary
Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer. Our groups
have pioneered liquid biopsy approaches for detection and characterization of cancer. Recently we have
developed a genome-wide approach for analysis of cfDNA fragmentation profiles called DELFI, DNA
evaluation of fragments for early interception. We demonstrated that fragmentation profiles of healthy
individuals from low coverage whole genome sequencing reflect nucleosomal patterns of white blood cells,
whereas patients with cancer had altered fragmentation profiles. Through the analysis of cell-free DNA
fragmentation patterns, we identified patients with localized cancer and this tool of early detection could result
in better patient outcomes. Lung cancer is the most lethal cancer in the world, and its incidence continues to
increase worldwide. There is an urgent, unmet clinical need for development of noninvasive approaches to
improve cancer screening for high-risk individuals and ultimately the general population. A clear
understanding of molecular changes along the pathway of lung tumorigenesis is critical for identifying
biomarkers related to carcinogenesis and tumor progression. Biomarker development for early detection of
lung cancer has broad clinical applications in screening as well as for distinguishing malignant from benign
pulmonary nodules. Tools to better predict the fate of early lesions non-invasively would be invaluable for
early detection of lung cancer, when curative approaches are more likely to succeed. Unlike targeted deep
sequencing approaches that would be cost prohibitive for broad use in a screening population, our approach
is affordable, highly scalable, and may lead to more effective strategies for clinical intervention. The recent
intersection of cancer genomics with novel noninvasive blood tests could revolutionize cancer screening.
The purpose of our proposed research is to study the origins and molecular characteristics of cell-free DNA
fragments along the progression of Lung Cancer, profiling these alterations in preneoplastic lung lesions
likely to progress to invasive cancer, and in treatable lung tumors, as well as in normal controls and in benign
lesions. We aim to implement new features to further optimize our DELFI molecular test in plasma. The
proposed plan is to test and validate our approach in both accrued samples and a prospective lung cancer
screening population. Ultimately, this approach already shows great promise as a pan-cancer early detection
strategy and we intend to expand our research in this direction in collaboration with other EDRN centers. We
envision that these analyses will be rapidly translated into the clinical setting, providing new noninvasive
approaches for early cancer detection.

## Key facts

- **NIH application ID:** 10889171
- **Project number:** 5U01CA271896-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DAVID SIDRANSKY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,001,112
- **Award type:** 5
- **Project period:** 2023-07-17 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889171

## Citation

> US National Institutes of Health, RePORTER application 10889171, DNA evaluation of fragments for early interception (DELFI) of Lung cancer (5U01CA271896-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889171. Licensed CC0.

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