Thursday, October 16, 2025 10/16/2025

Metastasis of PTEN Mutant Prostate Cancer

Award Number: R01CA275128
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Metastasis of PTEN Mutant Prostate Cancer - With an estimated 190,000 new diagnoses in 2020, Prostate Cancer (PC) is the second most frequent tumor diagnosed in men and the second leading cause of male cancer deaths in America. Approximately one in three men over the age of 50 shows histological evidence of this tumor, however only one in ten will be diagnosed with clinically signiﬁcant PC. Therapeutic options for localized PC are effective, however, metastatic PC is a yet incurable disease because standard of care anti-androgen therapy invariably results in incurable disease relapse. PTEN-TP53 loss is a most signiﬁcant event of human lethal metastatic PC as summarized by the PCF/SU2C International Prostate Cancer Dream Team (Armenia et al., 2018) and conﬁrmed by two decades of functional PC modeling in mouse. The central goal of this project is to understand what causes PTEN-mutant indolent prostate cancer (PC) to metastasize to different parts of the body and kill the patient. While the PCF/SU2C report signiﬁcant association of PTEN loss with loss of TP53, the deﬁnition of further genes that are signiﬁcantly co-mutated with PTEN has remained a problem. Importantly, such genes could point to pathways and principles that drive metastasis and/ or therapy resistance. We aim to solve this problem by combining single cell analysis of patient metastatic rapid autopsy samples with functional genetics and 3D whole organ imaging of lethal metastasis in mouse. We use a highly ﬂexible genetically engineered mouse (GEM) model of lethal, endogenous metastatic prostate cancer, termed RapidCaP. Spontaneous progression to lethal metastasis is seen in ~70% of Pten/Trp53-mutant RapidCaP, suggesting a critical stochastic pioneer event that switches a Pten/ Trp53 null tumor cell from indolence to metastatic escape, similar to a critical pioneering event that causes relapse after castration therapy. However, classical approaches can only capture and reveal the time and physical nature of these pioneering events when already thousands or millions of cells are involved. In Aim 1, we reveal, isolate, and analyze single pioneer cells in space and time. We combine RapidCaP with serial two photon tomography (STPT), which allows us to image whole organs at single cell resolution and construct a 3D map of the time course of escape from indolence and of metastatic relapse after therapy. This guides our isolation of cell types that then serve as validated proxies for pioneer cells of escape or relapse. Through Aim 2, we solve the PTEN co-mutation impasse and deﬁne genes co-deleted with PTEN through single cell whole genome analysis of human rapid autopsy samples. We prioritize candidates based on comprehensive functional molecular probing of already isolated pioneer cells in vitro. Through Aim 3, we develop two new modeling platforms for more ﬂexible validation of candidate genes and principles behind escape from indolence and relapse from castration therapy.


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 = $1,105,348 )
2025	2025	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Cancer Biology Research	001	4	9/3/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,105,348
2025	2024	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Cancer Biology Research	000	3	9/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,105,348

Issue Date FY: 2024 ( Subtotal = $525,040 )
2024	2024	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Cancer Biology Research	000	3	8/20/2024	NON-COMPETING CONTINUATION	$525,040
														Subtotal = $525,040

Issue Date FY: 2023 ( Subtotal = $541,620 )
2023	2023	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Cancer Biology Research	000	2	8/22/2023	NON-COMPETING CONTINUATION	$541,620
														Subtotal = $541,620

Issue Date FY: 2022 ( Subtotal = $529,446 )
2022	2022	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Cancer Biology Research	000	1	8/24/2022	NEW	$529,446
														Subtotal = $529,446

Grand Total All Awards = $2,701,454

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metastasis of PTEN Mutant Prostate Cancer

Award Number: R01CA275128

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer