# Fructose Metabolism as a Biomarker for Monitoring Hepatocellular Carcinoma

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $397,258

## Abstract

Project Summary/Abstract (Description)
Consistent with the mission of the funding announcement to use engineering principles to solve problems in biomedical
science, this research proposes to develop new tools to monitor hepatocellular carcinoma (HCC) based on changes in hepatic
fructose metabolism. HCC is a malignancy of the liver and the prognosis of the disease does not solely depend on tumor
stage but also on liver function. The prevalence of metabolic syndrome has also seen non-alcoholic fatty liver disease
(NAFLD) as the leading cause of HCC in the US. While there is an increase incidence of this HCC, there is an unmet need
for tolls that enable early detection and staging of HCC. This study proposes to develop new biomarkers to track cancer
progression based on the loss of fructose metabolism in HCC.
We hypothesize that fructose metabolism is lost in the development of liver cancer and can be used track HCC. This is
based on published literature and our recent experiments showing proteins involved in hepatic fructose metabolism
including ketohexokinase (KHK) are down regulated in HCC. These observations form the foundation of our hypothesis
that fructose metabolism is the preserve of the normal liver and is down regulated in liver cancer. Therefore, development
of a blood-based test to measure fructose levels in the blood will inform on hepatic function. A complementary metabolic
imaging biomarker based on hyperpolarized magnetic resonance imaging (HP-MRI) will provide real-time, spatial
information. HP-MRI is a new imaging technology that improves detection of 13C-labeled molecules, enabling non-invasive
quantification of metabolic flux and is currently undergoing clinical trials. In Aim 1, we will measure blood and tissue levels
of fructose after an intravenous fructose injection in a mouse model of HCC in a background of NAFLD. We will use mass
spectrometry, in a new collaboration with the School of Pharmacy. We will then investigate the mechanism of action of this
phenomenon by focusing on the transcription factor, hepatocyte nuclear factor 4 alpha (HNF4A). In Aim 2, we will optimize
polarization of [2-13C] fructose, to enable detection of KHK activity in normal and HCC mice.
This project proposes to develop innovative and quantitative methods to track HCC based on a novel biological observation
of altered liver metabolism in HCC. Investigators from diverse backgrounds such as biochemistry, metabolomics and MR
engineering have been assembled to ensure success. The completion of this project will deliver complementary, translatable
technologies for monitoring HCC.

## Key facts

- **NIH application ID:** 10056463
- **Project number:** 1R21CA245492-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Sui Seng Tee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,258
- **Award type:** 1
- **Project period:** 2020-07-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056463

## Citation

> US National Institutes of Health, RePORTER application 10056463, Fructose Metabolism as a Biomarker for Monitoring Hepatocellular Carcinoma (1R21CA245492-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10056463. Licensed CC0.

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