Tuesday, July 1, 2025 7/1/2025

Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivity

Award Number: U01CA274276
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivity - Abstract Unlike many cancers, pancreatic ductal adenocarcinoma (PDAC) is characterized by a hypoxic, nutrient- deprived, immunosuppressive tumor microenvironment (TME) and a fibrotic stroma that may impair treatment response. Recent single-cell studies suggest a complex interplay between malignant tumor cells and other cell types within the TME, with crosstalk between tumor and stromal cell types influencing malignant cell phenotypes, including responses to therapy. Understanding these interactions will provide insight into PDAC progression and therapy resistance. In particular, cancer-associated fibroblasts (CAFs) are a major non-immune cell component of the TME and are comprised of several distinct subtypes that vary based on tumor subtype and the surrounding microenvironmental niche. In this proposal, we bring together a multidisciplinary team of basic and translational investigators that will build upon our prior studies to investigate the Tumor-TME co-organizer model with a focus on interrogating interactions between PDAC tumor cells and CAFs in the TME. Specifically, we will examine the overarching hypothesis that reciprocal signaling between tumor cells and CAFs shapes malignant cell and CAF phenotypes in a context-specific manner that can be modulated by prior therapy and the organ-specific niche. We will leverage multiple built-in capabilities, including genetically engineered mouse models (GEMMs), patient- derived organoid (PDO) and matched fibroblast models, functional genetic screens and clinical trials with serial biopsies to study the PDAC TME continuum in disease progression and resistance to therapy. Specifically, we propose (1) to determine whether targeting organ-specific PDAC-CAF interactions enhances therapeutic responses, (2) to interrogate novel vulnerabilities resulting from tumor cell and CAF reprogramming during PDAC therapy, and (3) investigate whether TGFB blockade disrupts tumor cell-CAF crosstalk and sensitizes PDAC to chemotherapy. In pursuing these studies, we will work with other members of the PDAC Stromal Reprogramming Consortium (PSRC) to pursue collaborative studies to understand how PDAC and TME interactions program tumor progression and therapy responses.


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	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	000	3	4/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $985,172 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	001	3	9/25/2024	NON-COMPETING CONTINUATION	$0
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Biology Research	000	3	8/12/2024	NON-COMPETING CONTINUATION	$985,172
														Subtotal = $985,172

Issue Date FY: 2023 ( Subtotal = $1,037,023 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	8/31/2023	NON-COMPETING CONTINUATION	$1,037,023
														Subtotal = $1,037,023

Issue Date FY: 2022 ( Subtotal = $1,037,023 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	9/19/2022	NEW	$1,037,023
														Subtotal = $1,037,023

Grand Total All Awards = $3,059,218

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivity

Award Number: U01CA274276

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/19/2022

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