# Novel MUC1 Theranostic Peptides for Imaging and Treatment of Triple-Negative Breast Cancer

> **NIH NIH R37** · STANFORD UNIVERSITY · 2024 · $462,860

## Abstract

ABSTRACT.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer defined by a poor overall
prognosis, aggressive and early pattern of metastases, and a lack of treatments that lead to sustained disease
control. There is a critical need for molecular targeted treatments for patients with TNBC that are more effective,
have reduced side effects, and decrease the mortality associated with TNBC. Mucin-1 (MUC1) is overexpressed
and underglycosylated in 94% of TNBC and the receptor density is extremely high. The combination of the
modification of the glycosylation and overexpression allow tumor associated MUC1 distinguishable and
targetable from normal tissue. Targeted radionuclide therapy (TRT) is a molecular targeted treatment that
specifically uses radiolabeled moieties as biological targeting vectors intended to deliver localized cytotoxic
radiation to cancer cells that overexpress specific receptors, without harming normal cells. We propose to
combine the suitability of MUC1 as a therapeutic target in TNBC with the promising technique of TRT to develop
a novel theranostic peptide for diagnostic imaging and TRT of TNBC.
The aims of this proposal are to develop MUC1 targeted peptides that can successfully be applied for TRT,
exhibiting properties suitable for clinical translation. The advantages of peptides over previously studied antibody
radioisotope complexes include the superior pharmacokinetics, low immunogenicity, and ease of synthesis for
widespread application. In Aim 1 we will determine the mechanism and specificity of peptide binding, optimize
the incorporation of a metal chelator through various spacer moieties, and employ different cyclization strategies
to improve peptide affinity and stability. In Aim 2 we will radiolabel three peptide sequences with promising
binding affinities with gallium-68 and lutetium-177. We will complete a comprehensive analysis of binding and
internalization in TNBC cells, and determine in vivo tumor targeting properties and biodsitribution in mouse
models of TNBC. In Aim 3, we will advance the most promising peptide sequence, identified through quantitative
metrics, to therapeutic studies and determine the ability of MUC1 TRT to treat TNBC in mouse models. We will
additionally complete a preliminary safety assessment. Through these studies we will also understand any issues
related to proceeding with clinical translation of the MUC1 theranostic peptide for application in TNBC.
Given the morbidity and mortality associated with TNBC and the critical need for targeted treatments, this MUC1
TRT will have high impact for the treatment and management of TNBC. We will provide proof of concept that
MUC1 is a valid therapeutic target and that TRT can effectively treat TNBC. We intend for our results to lay the
foundation for subsequent development of randomized, controlled clinical trials that test this promising treatment
in patients with TNBC. If successful, this will be a significant step for...

## Key facts

- **NIH application ID:** 10767613
- **Project number:** 1R37CA278744-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Corinne Beinat
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,860
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767613

## Citation

> US National Institutes of Health, RePORTER application 10767613, Novel MUC1 Theranostic Peptides for Imaging and Treatment of Triple-Negative Breast Cancer (1R37CA278744-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10767613. Licensed CC0.

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