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Tumor-intrinsic and paracrine roles of endoglin in pancreatic cancer

Award Number: R01CA275036
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Tumor-intrinsic and paracrine roles of endoglin in pancreatic cancer - ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy featuring early metastasis, late onset of symptoms, and notorious resistance to existing therapies. A critically elusive aspect of this disease relates to the tumors which are often hypovascularized relative to other solid cancers, manifesting in poor perfusion and impaired drug delivery. In preliminary studies, we discovered that endoglin, normally an endothelial-specific TGF-beta coreceptor required for angiogenesis, is expressed as two variants in pancreatic cancer cells- the wildtype, which supports tumor-intrinsic growth and chemoresistance; and a novel splice variant with distinct structural features that gets secreted to inhibit tumor vascularization. To understand their interplay in the tumor microenvironment, we have generated a variety of cellular and pharmacologic reagents to interrogate the underlying mechanisms and their therapeutic potential. We propose to define novel paracrine mechanisms of TGF-beta signaling that suppress PDAC vascularization (Aim 1); and identify tumor-intrinsic endoglin pathways as critical therapeutic targets in PDAC (Aim 2); and determine the endoglin variants as distinct spatiotemporal targets during disease progression (Aim 3). Results from these studies will define TGF- beta-based mechanisms critical for PDAC tumor growth and vascularization and deliver clinically relevant data for improved patient-based therapeutics.


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 = $375,820 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Biology Research	000	3	6/25/2025	NON-COMPETING CONTINUATION	$375,820
														Subtotal = $375,820

Issue Date FY: 2024 ( Subtotal = $357,480 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Biology Research	000	2	7/19/2024	NON-COMPETING CONTINUATION	$357,480
														Subtotal = $357,480

Issue Date FY: 2023 ( Subtotal = $376,732 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Biology Research	000	1	7/28/2023	NEW	$376,732
														Subtotal = $376,732

Grand Total All Awards = $1,110,032

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Tumor-intrinsic and paracrine roles of endoglin in pancreatic cancer

Award Number: R01CA275036

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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