Wednesday, December 17, 2025 12/17/2025

Androgen Activation of Innate Immune Signaling to Enhance Prostate Cancer Immune Response

Award Number: R01CA243184
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Androgen Activation of Innate Immune Signaling to Enhance Prostate Cancer Immune Response - Bipolar androgen therapy (BAT) is a paradoxical approach for the treatment of castration-resistant prostate cancer (CRPC) whereby testosterone levels are rapidly cycled between supraphysiologic and castrate concentrations. Understanding how BAT works at the molecular and cellular levels might help in rationally combining BAT with other agents to achieve increased efficacy and tumor responses. Previous observations suggest that supraphysiological testosterone (SupraT) induce DNA double strand breaks (DSB). It has been speculated that if left unrepaired, DSBs may lead to cellular crisis and apoptosis. In this proposal, we provide novel evidence that unrepaired DSBs induced by SupraTs are routed to the autophagosomes where they activate cytoplasmic nucleic acid sensors that trigger the downstream interferon stimulated genes (ISGs) and innate immune pathways. Based on our preliminary data, we propose a novel idea that: i) Unrepaired DSBs induced by SupraTs are routed for specialized autophagic degradation termed nucleophagy; ii) SupraTs induced autophagosomal DNA can activate cytoplasmic DNA sensing pathways~ specifically the nucleic acid sensing pathway (cGAS-STING and RIG-I pathway); iii) Activation of nucleic acid sensing pathway by SupraTs would be more pronounced in prostate tumors that have DNA repair defect; and iv) BAT might activate innate and adaptive immune cells specially, in a subset of patients having DNA repair defect. In this proposal, we will determine the role of nucleic acid sensors in mediating immune signaling by SupraTs in PCa. Utilizing tumor biopsies from PCa patients receiving BAT, we will evaluate whether nucleic acid sensor mediated innate immune signaling serves as a molecular determinant of treatment response. To test our hypothesis, we will utilize several innovative tools and resources including CRISPR-Cas9 generated knockout cellular models, GeoMx Digital Spatial profiling of immune landscape in the tumor microenvironment, unique patient derived prostate cancer xenografts models, a humanized mouse models that has functional innate and adaptive immune cells, and serum and tumor biopsies from patients receiving BAT. We think these unique resources position us well to undertake the proposed work with immediate clinical impact. We have assembled a team of experts in basic and clinical prostate cancer biology and immunotherapy who will provide their unique expertise to successfully accomplish our goals. Successful completion of the proposed work will generate: a) mechanistic insights into modulation of immune response by SupraTs, b) valuable clinical insights into activation of immune cells by BAT, c) novel tumor- and serum-based markers that can be utilized for the development of biomarkers predictive of therapy response, and d) provide a rationale for strategically utilizing BAT to activate immune response and combine it with immunotherapeutics that empower the adaptive immune system such as immune checkpoint blockade and T-cell therapeutics to achieve synergy.


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 = $446,045 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	5	12/5/2025	NON-COMPETING CONTINUATION	$446,045
														Subtotal = $446,045

Issue Date FY: 2025 ( Subtotal = $1 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	4	2/17/2025	NON-COMPETING CONTINUATION	$1
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	001	4	6/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1

Issue Date FY: 2024 ( Subtotal = $498,873 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	001	3	4/17/2024	NON-COMPETING CONTINUATION	$26,258
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	3	12/12/2023	NON-COMPETING CONTINUATION	$472,615
														Subtotal = $498,873

Issue Date FY: 2023 ( Subtotal = $488,578 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	2	12/1/2022	NON-COMPETING CONTINUATION	$448,693
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	001	2	3/17/2023	NON-COMPETING CONTINUATION	$39,885
														Subtotal = $488,578

Issue Date FY: 2022 ( Subtotal = $527,817 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Biology Research	000	1	11/26/2021	NEW	$527,817
														Subtotal = $527,817

Grand Total All Awards = $1,961,314

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Androgen Activation of Innate Immune Signaling to Enhance Prostate Cancer Immune Response

Award Number: R01CA243184

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer