# Chemoprevention of Breast Cancer by Targeting Glucose Metabolism with HJC0152

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2022 · $535,020

## Abstract

SUMMARY
Chemoprevention of Breast Cancer by Targeting Glucose Metabolism with HJC0152
 About 60-70% of breast cancers (BCs) are estrogen receptor (ER)-positive BCs (EPBCs), and the
remaining 30-40% are ER-negative BCs (ENBCs). Currently available anti-ER-based chemopreventive
therapies, such as selective ER modulators and aromatase inhibitors, are effective in preventing only about
half of EPBCs and do not prevent any ENBCs, meaning that almost 60% of BCs cannot be prevented with
existing anti-ER-based preventive agents. In particular, the majority of ENBCs are triple-negative BCs
(TNBCs), which grow faster, spread earlier, and recur more often than other BC subtypes do, and the
incidence of TNBC is higher among young African American and Hispanic/Latina women and women with
BRCA1 mutations. BC survivors, particularly ENBC and TNBC survivors are at a predictable increased risk of
developing a new BC in the breasts. Thus, the prevention of BC in those “healthy” women and BC survivors
represents a huge, urgent but unmet need, since currently available preventive agents are anti-ER-based, and
is ineffective to protect women from developing BC. Those women or BC survivors will likely benefit most from
effective, non–ER-based preventive drugs. The proposed research will directly address this overarching
challenge by defining new intervention points and developing effective agents for preventing all BC subtypes.
We recently discovered a small molecule, HJC0152, which can modulate glucose metabolism and effectively
block premalignant lesions and ENBC/TNBC formation in transgenic mouse models of human ENBC. We
hypothesize that effective modulation, reprograming, and restoration of dysregulated glucose metabolism with
HJC0152 will reverse precancerous changes and block BC development. We will test this hypothesis through 3
specific aims. In Aim 1, we will determine the preventive efficacy of HJC0152 in ENBC and TNBC models in
various clinically relevant prevention settings. Preclinical assessments and safety profiling will also be
performed. In Aim 2, we will identify the physically interacting targets of HJC0152 that are essential to
ENBC/TNBC development through multiple approaches including bait-molecule affinity binding to capture
potential targets of HJC0152. In preliminary studies, we have identified a list of bona fide targets for HJC0152
for further investigation. In Aim 3, we will characterize and validate the top-ranked high-confidence target of
HJC0152, arginase, by performing affinity binding determination, co-complex of ligand-target interaction, gain-
/loss-of-function assessments, and expression determination experiments in breast cells and tumors. These
studies will elucidate the drivers of BC development and provide a solid foundation for further preclinical and
clinical development of HJC0152 as a non-ER-based preventive drug candidate. Given the demonstrated
preventive efficacy of HJC0152, low toxicity profiles, identification of high-c...

## Key facts

- **NIH application ID:** 10402887
- **Project number:** 5R01CA226001-05
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Qiang Shen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $535,020
- **Award type:** 5
- **Project period:** 2018-04-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402887

## Citation

> US National Institutes of Health, RePORTER application 10402887, Chemoprevention of Breast Cancer by Targeting Glucose Metabolism with HJC0152 (5R01CA226001-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10402887. Licensed CC0.

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