# Macrocycle inhibition of beta-catenin mediated transcription in prostate cancer

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $704,918

## Abstract

Project Summary
Among men, prostate cancer is the most prevalent form of cancer and the third most common cause of cancer-
related death. While patients with localized disease have a positive prognosis, those with metastatic disease
have a five-year survival rate of 30%. The main therapeutic target in prostate cancer is the androgen receptor
(AR). Most patients treated with anti-androgens will develop resistance and continue disease progression to
metastatic castration resistant prostate cancer (CRPC). Second-generation anti-androgens, including
enzalutamide and abiraterone, extend life expectancy, but eventually result in resistance to the treatment.
These findings highlight the need for new treatment approaches necessary to overcome or limit the
development of resistance. As many as 20% of aggressive prostate cancers have mutations resulting in
upregulation of Wnt/β-catenin signaling. β-catenin is a transcription factor that is activated in response to Wnt
pathway signaling. To cause changes in gene transcription β-catenin interacts with the DNA binding protein
called TCF. Importantly, recent analysis identified the Wnt/β-catenin pathway as the foremost differentially
modulated pathway among enzalutamide-resistant individuals. To target the Wnt/β-catenin pathway, we used
structure-based design of oligomeric macrocycles to identify new molecules that potently inhibit Wnt/β-catenin
signaling and the growth of prostate cancer cells. Our goal is to evaluate the ability of macrocycle 13, the lead
inhibitor identified in our screen, to suppress β-catenin signaling in castration resistant prostate cancer using in
vivo models of prostate cancer. We will also determine the impact of β-catenin inhibition on immune cells.

## Key facts

- **NIH application ID:** 10984643
- **Project number:** 1R01CA285624-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Susan K. Logan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $704,918
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984643

## Citation

> US National Institutes of Health, RePORTER application 10984643, Macrocycle inhibition of beta-catenin mediated transcription in prostate cancer (1R01CA285624-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984643. Licensed CC0.

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