# New approach based on enzyme stimulating of peptides for targeting drug resistance breast cancers

> **NIH NIH R16** · UNIVERSITY OF NORTH TEXAS · 2024 · $180,300

## Abstract

Abstract
Triple-negative breast cancer (TNBC) is a type of breast cancer that does not express the estrogen
receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2)
protein which accounts for 15–20 % of all breast cancer cases. TNBC tumors are generally larger, are
of higher grade, and are more aggressive than other breast cancer types. TNBC is unlikely to respond
to hormonal therapy medicines, including tamoxifen and aromatase inhibitors. TNBC also is unlikely to
respond to medicines that target the HER2 protein, such as Herceptin (trastuzumab). Treatment of
TNBC patients has been challenging due to the lack of molecular targets. Therefore, there is a critical
unmet need to develop more effective therapies for TNBC and drug-resistant breast cancers. The
development of new treatments would require radically different approaches that rely on enzymatic
reactions specific to TNBC cells rather than the cell receptors.
This proposal hypothesizes that properly designed peptide substrates of Eyes Absent enzyme (EYA)
can selectively inhibit TNBC cell growth by a self-assembling process. The central hypothesis is that
tyrosine phosphatase activity of EYA in TNBC could specifically convert the peptide therapeutics into
nanofibers and induce controlled apoptosis of TNBC cells. The preliminary data suggested that a
modified sequence of peptides with only one added amino acid could be de-phosphorylated by EYA
and self-assemble into nanostructures to inhibit the growth of TNBC cells (MDA-MB-231). In this
project, different peptide substrates of EYA will be synthesized by changing variable factors and the
correlation of structure to enzyme activity and cell apoptosis will be determined by focusing on the
following aims:
Aim 1: Design and synthesize self-assembling peptide substrates for EYA enzymes; Aim 2:
Determining the efficacy of peptide substrates for inhibiting TNBC in spheroid 3D cell cultures.
The correlation between the enzyme kinetic and the activity of nanostructures for targeting EYA will
be evaluated. Aim 3: The apoptosis response of the TNBC cells will be determined. This study will
lead to finding the potent peptide substrate and the effective dose for inhibiting TNBC cells with
apoptosis cell death.

## Key facts

- **NIH application ID:** 10909182
- **Project number:** 5R16GM150848-02
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS
- **Principal Investigator:** Neda Habibi
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $180,300
- **Award type:** 5
- **Project period:** 2023-08-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909182

## Citation

> US National Institutes of Health, RePORTER application 10909182, New approach based on enzyme stimulating of peptides for targeting drug resistance breast cancers (5R16GM150848-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909182. Licensed CC0.

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