# Hexokinase 2 in liver cancer

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $432,799

## Abstract

Project Summary
Targeting a protein or a protein activity that is present only in hepatocellular carcinoma
(HCC) cells and is required for HCC could be an ideal therapeutic approach that
selectively targets HCC and spares normal hepatocytes. One such protein is hexokinase
2 (HK2) that catalyzes the first committed step in glucose metabolism. HK2 is perhaps
the only glycolytic enzyme that is expressed in the cancer cells and not in their normal
matching cells. HK2 is expressed only in embryonic liver and not in the adult liver. In the
adult liver HK2 is ceased to be expressed and normal differentiated hepatocytes only
express the low affinity hexokinase, glucokinase (GK), as an adaptation to liver function.
However, HK2 is highly expressed in HCC cells while GK expression is suppressed. The
highly glycolytic HCC cells are therefore dependent on HK2, establishing HK2 as an
attractive selective target for HCC therapy. In a survey of 312 patient samples we found
a strong correlation between high level of HK2 expression, dysplasia, and carcinoma
regardless of the type or cause of HCC. Thus, despite the genetic heterogeneity of HCC,
the induction of HK2 expression and the shift from GK to HK2 are common events in
HCC. We found that systemic whole body deletion of HK2 in adult mice does not elicit
adverse physiological consequences and is therapeutic for breast and lung cancers in
mice. Because the only hexokinase expressed in HCC cells is HK2, it could be an ideal
target for HCC therapy. The ultimate goals of this grant application are to understand the
requirement of HK2 for the development of HCC and to examine the feasibility of HK2
inhibition for HCC therapy.

## Key facts

- **NIH application ID:** 9944460
- **Project number:** 5R01CA206167-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Nissim Hay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,799
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944460

## Citation

> US National Institutes of Health, RePORTER application 9944460, Hexokinase 2 in liver cancer (5R01CA206167-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9944460. Licensed CC0.

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