Tuesday, December 30, 2025 12/30/2025

The Delta Ecology of NSCLC Treatment

Award Number: U54CA274507
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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The Delta Ecology of NSCLC Treatment - Summary – Moffitt CSBC Proposal Overview The Moffitt CSBC proposal is focused on the essential and highly dynamical interplay between cancer cell evolution and the constantly changing ecology of the lung microenvironment. Tumors are not simply collections of mutated cells that grow in isolation. Rather, they respond to and modify both the physical microenvironment and a variety of host cells, and these changes in ecology (“∆-Ecology”) are key to understanding tumor progression and the response to therapy – particularly the development of resistance. Central to this proposal is quantifying, understanding, and actioning the change that occurs during treatment to both the tumor and non-tumor ecology in non-small cell lung cancer (NSCLC), which is the most common and among the most lethal of human cancers. We will define the ecological and evolutionary dynamics that govern NSCLC progression and treatment success or failure through 2 projects and 2 shared resource cores. Each project will focus on different D-Ecology dynamics in the presence of different driver mutations (RAS, EGFR, ALK) for which targeted therapy is available. Each project demonstrates our unifying theme of tight empirical/mathematical integration through the sequence of develop, predict, calibrate, test, optimize, and validate. Thus, each project begins with available clinical data followed by in silico (predict and optimize), in vitro (calibrate and test) and in vivo (validate) model systems leading to readily translatable treatment options. The mathematical and ecological Cores incorporate the mathematical and computational methods needed for bridging the projects. The Math Core will serve as the mechanistic model engine of the center, facilitating both spatial and non-spatial models of eco-evolutionary processes to generate and test hypotheses regarding ∆- Ecology. The Ecology Core serves as data repository and ecological analysis engine working in lockstep with the three Projects focused on different aspects of NSCLC ∆-Ecology (Immune and Stromal) to develop and apply spatial ecological models. These cores will serve our two projects: Project 1: Delta immune Ecology of NSCLC 1.1 Quantify the ∆-Ecology of patient samples pre- and on- treatment to predict outcomes; 1.2 Impact of KRAS inhibitor therapy with immunotherapy on lung tumor ecology; 1.3 Use predictive modeling to generate evolutionary inspired multi-agent treatment strategies. Project 2: Delta stromal Ecology of NSCLC 2.1 Decipher, in vivo, the ∆-Ecology of acquired resistance to targeted therapies in NSCLC; 2.2 Define the impact of stromal sheltering on the emergence of resistance and tumor growth relapse; 2.3 Discover optimal therapeutic strategies to suppress resistance.


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 = $2,165,301 )
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	002	3	9/17/2025	SUPPLEMENT FOR EXPANSION	$67,476
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	001	3	9/11/2025	NON-COMPETING CONTINUATION	$2,097,825
2025	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	000	2	4/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,165,301

Issue Date FY: 2024 ( Subtotal = $2,060,411 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	000	2	8/28/2024	NON-COMPETING CONTINUATION	$1,992,935
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	001	2	9/17/2024	SUPPLEMENT FOR EXPANSION	$67,476
														Subtotal = $2,060,411

Issue Date FY: 2023 ( Subtotal = $2,089,297 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Centers Support Grants	000	1	9/15/2023	NEW	$2,089,297
														Subtotal = $2,089,297

Grand Total All Awards = $6,315,009

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The Delta Ecology of NSCLC Treatment

Award Number: U54CA274507

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/15/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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