# Cell-Free Nucleic Acids for Early Treatment Response Assessment of Hepatocellular Cancer

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2021 · $214,949

## Abstract

Dr. Aadel Chaudhuri is an Assistant Professor of Radiation Oncology at Washington University. The NCI K08
award will provide the funding necessary to achieve important goals for his career development, by allowing
him to: 1) Demonstrate that circulating tumor DNA can be used as an MRD biomarker after definitive-intent
treatment of localized liver cancer, 2) To use circulating tumor DNA as an early response biomarker for liver
cancer immune checkpoint blockade, and 3) To infer mechanisms of immunotherapy response by
deconvolution of cell-free RNA confirmed by single cell sequencing. To oversee Dr. Chaudhuri's training, he
will be mentored by Dr. Dennis Hallahan, an established figure in cancer biology and radiation oncology, Dr.
Maximilian Diehn, an expert in cell-free nucleic acid translational research, and by Dr. Timothy Ley, a world-
renowned expert in cancer genomics. In addition to his mentors, Dr. Chaudhuri has assembled a group of
advisors/collaborators who will lend expertise to his proposed research on cell-free nucleic acids for response
assessment of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the number three cause of cancer death worldwide and stereotactic body
radiotherapy (SBRT) and interventional radiology (IR) ablation play major roles in the definitive management of
early stages of disease. This proposal aims to address major clinical challenges for HCC patients treated with
SBRT or IR ablation. First, there is no standard-of-care surveillance modality that can reliably detect molecular
residual disease (MRD) after completion of therapy. Second, loco-regional post-treatment inflammatory/fibrotic
tissue changes can often be difficult to distinguish from tumor recurrence on standard-of-care surveillance
imaging. Thirdly, there is no standard-of-care modality available for assessing immune checkpoint blockade
early. To address these clinical challenges, we plan to use a method for profiling cell-free DNA that my
mentor's laboratory developed called CAncer Personalized Profiling by deep Sequencing (CAPP-Seq),
which relies on capture-based next-generation sequencing, and an analogous method for profiling cell-
free RNA. CAPP-Seq allows ultrasensitive quantitation of circulating tumor DNA (ctDNA) and through tracking
of multiple mutations and integrated digital error suppression has a detection limit of ~10 parts per million. We
recently published that CAPP-Seq ctDNA analysis can reliably detect molecular residual disease (MRD) shortly
after localized lung cancer treatment completion, and can be used for immune checkpoint inhibitor early
response assessment for metastatic lung cancer (MS in preparation). We hypothesize that similar methods
can be applied to localized HCC to detect post-treatment MRD, and for response assessment and
mechanism elucidation for advanced HCC patients treated with immune checkpoint blockade.

## Key facts

- **NIH application ID:** 10151600
- **Project number:** 5K08CA238711-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Aadel Chaudhuri
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $214,949
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151600

## Citation

> US National Institutes of Health, RePORTER application 10151600, Cell-Free Nucleic Acids for Early Treatment Response Assessment of Hepatocellular Cancer (5K08CA238711-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10151600. Licensed CC0.

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