R01CA285624
Project Grant
Overview
Grant Description
Macrocycle Inhibition of Beta-Catenin Mediated Transcription in Prostate Cancer - 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/SS-CATENIN signaling. SS-CATENIN is a transcription factor that is activated in response to WNT pathway signaling. To cause changes in gene transcription SS-CATENIN interacts with the DNA binding protein called TCF.
Importantly, recent analysis identified the WNT/SS-CATENIN pathway as the foremost differentially modulated pathway among enzalutamide-resistant individuals. To target the WNT/SS-CATENIN pathway, we used structure-based design of oligomeric macrocycles to identify new molecules that potently inhibit WNT/SS-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 SS-CATENIN signaling in castration resistant prostate cancer using in vivo models of prostate cancer. We will also determine the impact of SS-CATENIN inhibition on immune cells.
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/SS-CATENIN signaling. SS-CATENIN is a transcription factor that is activated in response to WNT pathway signaling. To cause changes in gene transcription SS-CATENIN interacts with the DNA binding protein called TCF.
Importantly, recent analysis identified the WNT/SS-CATENIN pathway as the foremost differentially modulated pathway among enzalutamide-resistant individuals. To target the WNT/SS-CATENIN pathway, we used structure-based design of oligomeric macrocycles to identify new molecules that potently inhibit WNT/SS-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 SS-CATENIN signaling in castration resistant prostate cancer using in vivo models of prostate cancer. We will also determine the impact of SS-CATENIN inhibition on immune cells.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
New York,
New York
100168367
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 385% from $704,918 to $3,419,009.
New York University was awarded
Macrocycle Inhibition Prostate Cancer: Targeting SS-CATENIN Signaling
Project Grant R01CA285624
worth $3,419,009
from National Cancer Institute in June 2024 with work to be completed primarily in New York New York United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.395 Cancer Treatment Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/22/26
Period of Performance
6/1/24
Start Date
5/31/29
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01CA285624
Additional Detail
Award ID FAIN
R01CA285624
SAI Number
R01CA285624-2225383809
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
75NC00 NIH National Cancer Institute
Funding Office
75NC00 NIH National Cancer Institute
Awardee UEI
M5SZJ6VHUHN8
Awardee CAGE
3D476
Performance District
NY-12
Senators
Kirsten Gillibrand
Charles Schumer
Charles Schumer
Modified: 6/22/26