Thursday, October 2, 2025 10/2/2025

Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage Plasticity

Award Number: R01CA266452
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage Plasticity - SUMMARY/ABSTRACT The AR may be the earliest known example of a lineage oncogene: a master regulator of cell survival and growth to which neoplastic cells derived from prostate epithelium are addicted. Recognizing this unique feature, concerted efforts have focused on developing therapeutics capable of suppressing AR signaling. Androgen deprivation therapy (ADT) and AR pathway signaling inhibitors (ARSI) produce dramatic responses in the vast majority of patients with metastatic PC (mPC). Unfortunately, these responses are not accompanied by cures, with near universal development of treatment resistance. Studies from our group and others have determined that an increasing fraction of mPCs resisting AR pathway inhibition lose AR activity and gain a spectrum of new phenotypes, each of which exhibit an aggressive clinical course with limited treatment options. The processes by which tumor cells switch lineages under treatment pressure is not well understood. Determining the mechanisms that permit or drive this lineage plasticity may identify new treatment strategies. This proposal is designed to address a major clinical problem whereby AR pathway inhibition promotes tumor cell plasticity. We will test the hypothesis that targeting permissive epigenetic factors or lineage determinants together with AR pathway inhibition will prevent lineage-redirection, prolong response rates overall, and cure a subset of advanced prostate cancers. AIM 1. Identify the key determinants and permissive factors that promote a lineage switch from conventional AR- driven prostate cancer to new phenotypes following AR-directed treatment. AIM 2. Determine if modulating factors that drive or permit lineage specification can prevent, delay, or reverse resistance to AR pathway inhibition. AIM 3. Determine if co-targeting characteristics of re-directed lineages that emerge in the context of lineage switching will prolong responses to AR pathway inhibition. In order for effective therapeutics to be developed that can adequately address this new class of malignancy, the pathways permitting or driving lineage conversion must first be clearly defined; this project aims to elucidate those underlying mechanisms.


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 = $402,600 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	4	7/1/2025	NON-COMPETING CONTINUATION	$402,600
														Subtotal = $402,600

Issue Date FY: 2024 ( Subtotal = $382,471 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	3	6/18/2024	NON-COMPETING CONTINUATION	$382,471
														Subtotal = $382,471

Issue Date FY: 2023 ( Subtotal = $394,548 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	2	7/10/2023	NON-COMPETING CONTINUATION	$394,548
														Subtotal = $394,548

Issue Date FY: 2022 ( Subtotal = $402,600 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	1	6/20/2022	NEW	$402,600
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	1	6/29/2022	NEW	$0
														Subtotal = $402,600

Grand Total All Awards = $1,582,219

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage Plasticity

Award Number: R01CA266452

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer