Thursday, July 3, 2025 7/3/2025

OVERCOMING STROMAL BARRIERS TO THERAPEUTICS IN PANCREAS CANCER

Award Number: R01CA161112
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/11/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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OVERCOMING STROMAL BARRIERS TO THERAPEUTICS IN PANCREAS CANCER - PROJECT SUMMARY Pancreatic ductal adenocarcinomas (PDA) are unrivaled in their lethality. PDAs have the highest 1- year, 5-year, and 10-year mortalities of any cancer and are expected to become the second-leading cause of cancer-related death by 2030. An invasive PDA represents the coordinated evolution of cell- intrinsic and extrinsic processes and capabilities that subvert and repurpose the dictums of normal tissue composition, architecture, and physiology to foster unbridled growth and colonization. This new organizational entity is constructed largely at the behest of the mutated epithelial cell. The resulting PDA neo-organ contains a minority of tumor epithelial cells amidst a heterogeneous sea of non- epithelial cells; a complex interstitial stew of proteins, proteoglycans and glycosaminoglycans, together with both freely mobile and complexed water; and a paucity of vessels that otherwise resemble a normal vasculature in lacking fenestrae or interendothelial junctions, but that are collapsed under intense interstitial pressures. We have undertaken a systematic exploration of the cell autonomous and non-cell autonomous processes that drive PDA pathogenesis and resistance. We have developed genetically engineered animal models that faithfully recapitulate the clinical syndrome, metastatic behavior, histopathology and molecular features of the human disease as primary platforms to both uncover critical principles of disease biology and to rigorously test strategies to overcome them. Through such investigations we have identified unusually high concentrations of intratumoral hyaluronan (HA) as the primary culprit in the extraordinarily elevated interstitial pressures in PDA that, in turn, cause the vascular collapse and hypoperfusion characteristic of this disease. The stromal barrier to perfusion also serves as a primary mechanism of drug resistance in limiting the penetration of systemically delivered agents. We have additionally identified multiple mechanisms of immune suppression that prevent the development of an endogenous effector T cell response. Collectively, these unique aspects of stromal biology in PDA conspire to create a drug- and immune-privileged sanctuary for unimpeded growth of the pancreas cancer cell. Very recently, we have elaborated strategies to overcome critical aspects of these physical and immunological barriers to therapy revealing a perhaps unexpected degree of vulnerability once the barriers are breached. We describe a series of continuing investigations into this overarching strategy of stromal re-engineering to build upon the significant inroads made – and the important lessons learned – in the hopes of radically transforming the approach and prognosis for this formidable disease.


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 = $463,532 )
2025	2025	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Cancer Treatment Research	002	16	5/23/2025	NON-COMPETING CONTINUATION	$463,532
2025	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Cancer Treatment Research	001	13	1/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$48,574
2025	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	12	1/21/2025	COMPETING CONTINUATION	-$48,574
														Subtotal = $463,532

Issue Date FY: 2024 ( Subtotal = $448,893 )
2024	2024	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Cancer Treatment Research	000	15	5/23/2024	NON-COMPETING CONTINUATION	$448,893
														Subtotal = $448,893

Issue Date FY: 2023 ( Subtotal = $497,998 )
2023	2023	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Cancer Treatment Research	004	14	9/6/2023	NON-COMPETING CONTINUATION	$497,998
2023	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	12	5/19/2023	COMPETING CONTINUATION	$0
2023	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Cancer Treatment Research	003	13	6/22/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$322,912
2023	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	002	12	6/22/2023	COMPETING CONTINUATION	-$322,912
2023	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	11	5/19/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $497,998

Issue Date FY: 2022 ( Subtotal = $588,480 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	004	12	8/11/2022	COMPETING CONTINUATION	$588,480
2022	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	003	11	8/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$7
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	002	10	8/8/2022	NON-COMPETING CONTINUATION	-$7
2022	2020	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	11	6/6/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	10	6/6/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $588,480

Issue Date FY: 2020 ( Subtotal = $513,402 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	10	7/13/2020	NON-COMPETING CONTINUATION	$513,402
														Subtotal = $513,402

Issue Date FY: 2019 ( Subtotal = $497,999 )
2019	2019	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	9	7/18/2019	NON-COMPETING CONTINUATION	$497,999
														Subtotal = $497,999

Issue Date FY: 2018 ( Subtotal = $513,402 )
2018	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	8	7/27/2018	NON-COMPETING CONTINUATION	$513,402
														Subtotal = $513,402

Issue Date FY: 2017 ( Subtotal = $620,121 )
2017	2017	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	002	7	8/9/2017	NON-COMPETING CONTINUATION	$520,121
2017	2017	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	003	7	9/8/2017	NON-COMPETING CONTINUATION	$100,000
2017	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	6	1/3/2017	COMPETING CONTINUATION	$18,454
2017	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	5	1/3/2017	NON-COMPETING CONTINUATION	-$18,454
														Subtotal = $620,121

Issue Date FY: 2016 ( Subtotal = $525,536 )
2016	2016	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	001	6	8/1/2016	COMPETING CONTINUATION	$525,536
2016	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	5	7/26/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $525,536

Issue Date FY: 2015 ( Subtotal = $506,216 )
2015	2015	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	5	7/10/2015	NON-COMPETING CONTINUATION	$506,216
														Subtotal = $506,216

Issue Date FY: 2014 ( Subtotal = $494,110 )
2014	2014	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	4	7/14/2014	NON-COMPETING CONTINUATION	$494,110
														Subtotal = $494,110

Issue Date FY: 2013 ( Subtotal = $479,510 )
2013	2013	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	3	7/11/2013	NON-COMPETING CONTINUATION	$479,510
														Subtotal = $479,510

Issue Date FY: 2012 ( Subtotal = $509,832 )
2012	2012	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	2	7/18/2012	NON-COMPETING CONTINUATION	$509,832
														Subtotal = $509,832

Issue Date FY: 2011 ( Subtotal = $524,117 )
2011	2011	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE NO J6-330	SEATTLE	WA	98109	KING	USA	Cancer Treatment Research	000	1	9/22/2011	NEW	$524,117
														Subtotal = $524,117

Grand Total All Awards = $7,183,148

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OVERCOMING STROMAL BARRIERS TO THERAPEUTICS IN PANCREAS CANCER

Award Number: R01CA161112

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/11/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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