Thursday, July 3, 2025 7/3/2025

Architecture and Trajectory of Acquired Resistance to Therapy in AML

Award Number: U54CA224019
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Architecture and Trajectory of Acquired Resistance to Therapy in AML - PROJECT SUMMARY: Overall The long-term goal of this Program is to define mechanisms of acquired drug resistance in acute myeloid leukemia (AML) so that novel drug combinations can be deployed to prevent disease relapse and improve patient outcomes. The overall five-year survival rate for AML remains 20%, an outcome that has not changed for several decades. Although seven new regimens have been approved for AML in recent years, the improved initial remission rates with these therapies do not lead to durable outcomes. Disease relapse is fueled by a complex cross-talk of tumor cells adapting with support from the bone marrow microenvironment. The investigators of this proposed ARTNet Center have collaborated for 15+ years, including as a Center in the DRSN consortium – the predecessor to ARTNet. Our prior work has involved development of the largest-to-date functional genomic dataset on AML patient samples, genome-wide CRISPR screens, broad studies of AML interactions with stromal and immune cells, and testing of diverse drug combinations. These studies have led to >150 collaborative publications, continuous collaborative funding for 15+ years, creation of numerous large datasets deposited into public repositories, and translation of findings into numerous clinical trials. Our overarching hypothesis is that the architecture of acquired drug resistance is governed by temporal extrinsic and intrinsic factors and elucidating this trajectory will allow for the identification of properly timed therapeutic strategies to stave off acquired resistance and stay ahead of tumor evolution and adaptation. This hypothesis will be tested through three well integrated Projects addressing the following questions: 1) How does AML tumor cell intrinsic biology adapt to evade therapeutic pressure? We will use genome-wide CRISPR platforms as well as long-term progenitor expansion of primary AML patient samples to understand feedback pathways and shifting epigenetic and cell state landscapes that can drive acquired drug resistance. 2) How does the stromal and immune microenvironment govern drug resistance? We will use co-culture and advanced bone marrow models to perform genome-wide screens and test the impact of single-agents on AML-microenvironment cross-talk. Through computational modeling, we will nominate targeting strategies to mitigate tumor extrinsic resistance signals and boost immune anti-tumor responses. 3) How can resistance signatures and drug combinations be effectively clinically translated? We will use high-throughput and advanced, engineered models of human bone marrow to test and prioritize drug combinations from targets in Projects 1 and 2. We will also study longitudinal specimens from patients enrolled on ongoing clinical trials. All of these data will inform and refine the work of Projects 1 and 2. Our Center will be supported by an Administrative Core and a Functional Phenotyping Core. Collectively, we will develop a comprehensive understanding of acquired drug resistance in AML and identify new regimens to treat patients at the earliest possible stage, prevent relapse, and achieve durable remissions.


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 = $0 )
2025	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	7	12/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,243,548 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	005	7	8/30/2024	NON-COMPETING CONTINUATION	$1,243,548
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	006	7	9/25/2024	NON-COMPETING CONTINUATION	$0
2024	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	004	6	8/30/2024	NON-COMPETING CONTINUATION	$0
2024	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	003	6	12/14/2023	NON-COMPETING CONTINUATION	$0
2024	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	5	10/30/2023	COMPETING CONTINUATION	$2
2024	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	4	10/30/2023	NON-COMPETING CONTINUATION	-$1
2024	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	4	10/30/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,243,548

Issue Date FY: 2023 ( Subtotal = $1,308,998 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	6	9/8/2023	NON-COMPETING CONTINUATION	$1,308,998
														Subtotal = $1,308,998

Issue Date FY: 2022 ( Subtotal = $1,308,998 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	5	8/15/2022	COMPETING CONTINUATION	$1,308,998
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	4	8/5/2022	NON-COMPETING CONTINUATION	$0
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	4	7/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,308,998

Issue Date FY: 2021 ( Subtotal = $1,248,331 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	4	9/1/2021	SUPPLEMENT FOR EXPANSION	$93,333
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	4	8/27/2021	NON-COMPETING CONTINUATION	$1,154,998
2021	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	3	8/3/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,248,331

Issue Date FY: 2020 ( Subtotal = $1,154,998 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	3	8/28/2020	NON-COMPETING CONTINUATION	$1,154,998
2020	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	2	3/31/2020	EXTENSION WITH OR WITHOUT FUNDS	$199,976
2020	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	3/31/2020	NEW	-$199,976
														Subtotal = $1,154,998

Issue Date FY: 2019 ( Subtotal = $1,248,330 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	2	9/11/2019	EXTENSION WITH OR WITHOUT FUNDS	$93,332
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	9/6/2019	EXTENSION WITH OR WITHOUT FUNDS	$1,154,998
														Subtotal = $1,248,330

Issue Date FY: 2017 ( Subtotal = $2,309,994 )
2017	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	9/25/2017	NEW	$2,309,994
														Subtotal = $2,309,994

Grand Total All Awards = $9,823,197

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Architecture and Trajectory of Acquired Resistance to Therapy in AML

Award Number: U54CA224019

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2017

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