Friday, December 12, 2025 12/12/2025

Overcoming mechanisms of PTPN1 driving therapy- and castration- resistant prostate cancer with novel theranostics

Award Number: R01CA295762
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2029

Group Awards By:

View Award Description

Overcoming mechanisms of PTPN1 driving therapy- and castration- resistant prostate cancer with novel theranostics - Project Summary/Abstract Overwhelming data from clinical experience clearly indicate that the recurrent therapy- and castration-resistant prostate cancer (t-CRPC) is responsible for the majority of these deaths because these cells exhibit resistant phenotype to hormonal therapy as well as conventional chemotherapy. Thus, new therapeutic target(s) based on molecular mechanisms leading to resistant phenotype is urgently needed for prolong the survival of prostate cancer (PCa) patients. More than 25% of the metastatic CRPC patients on highly potent new-generation anti-androgen therapies end up with neuroendocrine prostate cancer (NEPC). Currently, NEPC is considered as an end stage disease because only few chemotherapeutics for NEPC with unsatisfied outcome. From several tissue culture and transgenic animal models, data suggest that hormonal therapy promotes androgen-dependent prostate adenocarcinoma (ADPC) cells to undergo transdifferentiation then become therapy resistant NEPC. Nevertheless, the underlying molecular mechanism remain largely uncharacterized. In this study, we provide strong evidence that the protein tyrosine phosphatase non-receptor 1 (PTPN1) plays a critical role in PCa transdifferentiation. For example, Increased PTPN1 expression in ADPC promotes the onset of NEPC. In contrast, knocking down PTPN1 expression in NEPC cells can restore ADPC phenotype. Thus, this project is to examine the regulation of PTPN1 gene expression by anti- androgens and unveil the reciprocal regulatory network among PTPN1-androgen receptor- RE1- silencing transcriptional factor then identify the downstream effector(s) of PTPN1 in promoting NEPC. Most importantly, it is to develop a new NEPC-specific theranostic strategy by engineering NEPC-specific small drug conjugate with molecular imaging capabilities. The ultimate goal is to explore clinical translation by formulating a new therapeutic regimen with PTPN1 theranostics and anti-androgen agent in clinically relevant animal models. The outcome gained from this project will revolutionize the current concept of recurrent t-CRPC therapy in order to improve overall survival of patients.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $427,403 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Treatment Research	000	2	12/5/2025	NON-COMPETING CONTINUATION	$427,403
														Subtotal = $427,403

Issue Date FY: 2025 ( Subtotal = $472,458 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cancer Treatment Research	000	1	11/29/2024	NEW	$472,458
														Subtotal = $472,458

Grand Total All Awards = $899,861

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Overcoming mechanisms of PTPN1 driving therapy- and castration- resistant prostate cancer with novel theranostics

Award Number: R01CA295762

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer