Integrating tumor and stroma to understand and predict treatment response

Active Cooperative Agreement Awarded Last action

Award ID
U01CA274298
Recipient
Awarding agency
Obligated
$8,604,015

Award facts

Assistance listing
93.396 Cancer Biology Research
Completion date 83% complete
Place of performance
Chapel Hill, NC 27599, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

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.

Transactions

Action Obligated Date
Amendment $872,331
Amendment $0
Amendment $0
Amendment $0
Amendment $0
Amendment $914,890
Amendment $914,890
Amendment -$869,831
Amendment $85,780
Amendment $869,831
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Amendment $90,295
Amendment $90,295
Amendment Effect of JAK and RIPK2 inhibition on CAF and cancer cell crosstalk $15,050
Amendment $15,050
Amendment $15,050
Amendment $924,643
Amendment Effect of JAK and RIPK2 inhibition on CAF and cancer cell crosstalk $924,643
Amendment $924,643
Amendment $924,643
Amendment $945,906
Original award $945,906
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Subawards

Subrecipient Amount Awarded
Honorhealth At HonorHealth, patient samples will be provided from investigator-initiated trials (IIT’s) in pancreatic ductal adenocarcinoma. The trials include… $44,997
The Ohio State University The Ohio State University research team will enroll patients to undergo pre and post-treatment biopsies and will provide UNCCH with either snap frozen or… $240,131
Henry Ford Health System The research team at Henry Ford Health Systems will provide their expertise of best practices based on previous work in cancer associate fibroblasts (CAF) and… $55,439
University Of Rochester University of Rochester will provide either de-identified tissue or genomic datasets from paired biopsy specimens derived from ongoing clinical studies.… $62,952
The Medical College Of Wisconsin, Inc. The Medical College of Wisconsin research team will enroll approximately 87 patients who will undergo pre and post treatment biopsies. Deidentified samples of… $276,473

Quick answers

Who received award U01CA274298?

U01CA274298 was awarded to University Of North Carolina At Chapel Hill by National Cancer Institute (National Institutes of Health) on September 1, 2022.

How much is award U01CA274298 worth?

$8,604,015 has been obligated on U01CA274298.

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