Saturday, November 1, 2025 11/1/2025

The stromal microenvironment as a co-organizer of bladder carcinogenesis and progression

Award Number: U54CA274375
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/22/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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The stromal microenvironment as a co-organizer of bladder carcinogenesis and progression - OVERALL PROJECT SUMMARY Bladder cancer (BC) is the second most common urologic malignancy affecting 573,278 people worldwide in 2020. Pathologically, BC is diagnosed as non-muscle-invasive (NMI) and muscle-invasive (MI) disease. Here we define early bladder lesions as NMIBC. Major clinical gaps in NMIBC include i) lack of mechanistic insights defining NMIBC progression, and ii) lack of platform for risk stratification of NMIBC that recur but never progress (“non-progressors”), from those that progresses into MIBC (“progressors”) and consequently demonstrate poor prognosis. The goal of our Center is to tackle this clinical issue by deciphering the underlying mechanisms restraining or promoting the progression of early lesions (Project 1 & 2), and to leverage this novel biology as candidate biomarkers to risk-stratify aggressive NMIBC (Project 3). This proposal seeks to shift the current research paradigm in the field of NMIBC, by proposing a conceptually innovative tug-of-war between a tumor- restraining (Project 1) and a tumor-promoting mechanism (Project 2) in determining the outcome of early bladder lesions/NMIBC in becoming “progressors” or “non-progressors” (Project 3). Clinically, why “non-progressors” often recur but seldom progress, and what are the driving forces advancing “progressors” into MIBC with poor survival remain fundamental questions in field. Our tug-of-war hypothesis with two opposing forces is conceptually different to most other studies, which primarily focus on one side of the coin. Further, the integration of knowledge from Project 1 and 2 as a unified spatial proteomics and transcriptomics map by the Shared Resource Core will reveal spatial and temporal relationships between distinct fibroblast populations with opposing functions, their physical interactions with tumor and immune cell clusters, as well as their relationship to the biomarkers from Project 3. Benchmark of success: The knowledge gained here will shift clinical practice paradigm, by informing future NIMBC management through 1) the development of novel urinary profiling strategies that could risk stratify aggressive NMIBC (Project 1-3); 2) the identification of targets for future precision intervention, either by enhancing/sustaining the tumor-restraining mechanisms (Project 1) and/or inhibiting the tumor-promoting mechanisms (Project 2). The overall success of our program is further ensured by an extraordinary multi-investigator team that integrates three “organ-specific” bladder cancer investigators within Cedars-Sinai Medical Center. All have active R01s and individual NCI-funding track record in performing basic science research, translational bladder cancer research, or leading multi-center clinical trials on the discovery and validation of biomarkers. Finally, they propose to collect valuable retrospective and prospective NMIBC cohorts, which are essential to address the clinical questions posed within this proposal and will become available to the research community as a shared resource to advance the field.


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: 2025 ( Subtotal = $1,646,006 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	4	9/18/2025	NON-COMPETING CONTINUATION	$1,646,006
2025	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	3	10/18/2024	SUPPLEMENT FOR EXPANSION	$0
2025	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	3	10/11/2024	NON-COMPETING CONTINUATION	$0
2025	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	2	11/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $1,646,006

Issue Date FY: 2024 ( Subtotal = $1,739,452 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	3	9/11/2024	NON-COMPETING CONTINUATION	$1,564,827
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	004	3	9/17/2024	SUPPLEMENT FOR EXPANSION	$174,625
2024	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	2	12/5/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,745,043
2024	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	2	1/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Centers Support Grants	000	1	12/5/2023	NEW	-$1,745,043
														Subtotal = $1,739,452

Issue Date FY: 2023 ( Subtotal = $1,741,391 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	2	9/21/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,657,891
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	2	9/22/2023	SUPPLEMENT FOR EXPANSION	$83,500
2023	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Centers Support Grants	000	1	9/21/2023	NEW	$0
														Subtotal = $1,741,391

Issue Date FY: 2022 ( Subtotal = $1,745,043 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Centers Support Grants	000	1	9/22/2022	NEW	$1,745,043
														Subtotal = $1,745,043

Grand Total All Awards = $6,871,892

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The stromal microenvironment as a co-organizer of bladder carcinogenesis and progression

Award Number: U54CA274375

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/22/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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