Tuesday, October 21, 2025 10/21/2025

Integrating tumor and stroma to understand and predict treatment response

Award Number: U01CA274298
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Integrating tumor and stroma to understand and predict treatment response - ABSTRACT Through novel deconvolution approaches for bulk RNA sequencing analysis, we identified two tumor-intrinsic subtypes of PDAC (basal and classical) that we have confirmed, are robust, replicable, prognostic and predictive of treatment response. We found that the basal subtype is consistently associated with poor outcome and have shown, through analysis of two clinical trials, that patients with basal subtype tumors do not respond to the 1st-line therapy FOLFIRINOX. These results strongly support the idea that molecular subtypes may be used to select treatment. Given the impact of our tumor-intrinsic subtypes on therapy response, we developed a single sample classifier, PurIST, that is now a CLIA certified assay and being evaluated as an integral marker for treatment selection in a clinical trial. In parallel, we developed a de novo approach, DECODER to deconvolve bulk tumors into compartments that allows us to determine tumor and TME specific characteristics in patients. Using the deconvolution approaches that led us to identify tumor-intrinsic subtypes, we have found two types of PDAC stroma: activated, and normal where patients with activated stroma have shorter survival. We have shown that CAFs are the contributory cells in activated stroma. Patients can be found to have a combination of tumor/stroma subtypes and the combinations have different impacts on outcome, suggesting that it is critically important to understand tumor-stroma interactions and how they affect treatment response. Similarly, we find that i/myCAF may differentially educate basal vs. classical subtype lines Our findings provide strong support for our central hypothesis that CAFs and tumor cells have interactions that together may alter tumor progression and response, making it critical that we understand the heterogeneity of the stroma, and specifically CAFs, their interaction with the tumor, for tumor-stroma context specific treatment response. Our team is uniquely positioned to comprehensively characterize CAF/NAF-tumor heterogeneity and interactions, response to treatment, and develop an integrative CAF-tumor subtype classifier to predict treatment response of patients in standard of care, stroma and immune modulating trials.


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 = $914,890 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	000	4	9/19/2025	NON-COMPETING CONTINUATION	$914,890
2025	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	001	3	9/24/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $914,890

Issue Date FY: 2024 ( Subtotal = $955,611 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	001	3	8/7/2024	NON-COMPETING CONTINUATION	$869,831
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	003	3	9/25/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	002	3	8/8/2024	SUPPLEMENT FOR EXPANSION	$85,780
2024	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	3/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $955,611

Issue Date FY: 2023 ( Subtotal = $1,029,988 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	001	1	8/23/2023	SUPPLEMENT FOR EXPANSION	$15,050
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Cancer Biology Research	002	2	9/14/2023	SUPPLEMENT FOR EXPANSION	$90,295
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	8/14/2023	NON-COMPETING CONTINUATION	$924,643
														Subtotal = $1,029,988

Issue Date FY: 2022 ( Subtotal = $945,906 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	8/31/2022	NEW	$945,906
														Subtotal = $945,906

Grand Total All Awards = $3,846,395

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Integrating tumor and stroma to understand and predict treatment response

Award Number: U01CA274298

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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