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Identifying Metabolic Vulnerabilities in Lung Cancer

Award Number: P01CA250984
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/25/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Identifying Metabolic Vulnerabilities in Lung Cancer - OVERALL PROJECT SUMMARY IDENTIFYING METABOLIC VULNERABILITIES IN LUNG CANCER Lung Cancer is the most common cause of cancer deaths world-wide. Tyrosine kinase inhibitors and immunotherapy have been shown to be effective in a subset of patients; however, the overall survival rate for this disease remains low especially for metastatic disease. Moreover, small cell lung cancer (SCLC) patients have a poor prognosis, and there especially exists a gap in knowledge in understanding SCLC and identifying effective therapeutic strategies. Our goal in this proposal is to understand the underlying biology of key drivers in lung cancer by identifying metabolic vulnerabilities that can ultimately be used as single agents or combined with immunotherapy to target lung cancer therapeutically. We will achieve this goal by engaging experts that have developed preclinical models with common molecular signatures in non-small cell (NSCLC) and small cell lung cancer (SCLC) and cutting-edge metabolomics. We have an active and collaborative group that meets twice monthly with projects and manuscripts that are co-authored by the leaders of each project and core. Additionally, our Program Project Grant (PPG) team is located at Moffitt Cancer Center, which is an ideal place to study the pathogenesis of lung cancer. Florida is number 2 in the country in terms of newly diagnosed lung cancer patients. Moffitt treats 10% of these cases. The PPG consists of four projects and four cores. These projects and cores collaborate and synergize to meet four objectives: i. To identify metabolic vulnerabilities in lung cancers through integrative analysis of in vivo and ex vivo models with common molecular signatures, including p53, NRF2/KEAP1, and MYC (Project #1, led by Dr. Flores, Project #2, led by Dr. DeNicola, Project #3, led by Drs. Cleveland and Haura, and Project #4, led by Dr. Rodriguez with support from the Administrative Core #1, led by Drs. Flores and Haura, Preclinical Models and Pathology Core #2, led by Drs. Cress and Karreth, Metabolism Core #3, led by Dr. Koomen, and Data Science Core #4, led by Dr. Fridley), ii. To identify metabolic vulnerabilities that synergize with immunotherapy through examining the tumor microenvironment and gaining a deep molecular understanding of myeloid derived suppressor cells (MDSCs). (Project #4 in collaboration with Projects #1 and #2 and Core #2), iii. To build mouse models as a platform to understand the metabolic pathways utilized by lung cancers with different genetic signatures and to assess therapeutic strategies for lung cancer. (Core #2 supporting Projects #1-4), and iv. To share resources and data locally and globally to obtain an integrated molecular understanding of metabolic vulnerabilities in lung cancer. (Core #4 leading efforts from All Projects and Cores).


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 = $2,032,950 )
2025	2025	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Biology Research	000	5	6/25/2025	NON-COMPETING CONTINUATION	$2,032,950
														Subtotal = $2,032,950

Issue Date FY: 2024 ( Subtotal = $1,951,918 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Biology Research	000	4	7/1/2024	NON-COMPETING CONTINUATION	$1,951,918
														Subtotal = $1,951,918

Issue Date FY: 2023 ( Subtotal = $2,019,244 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Biology Research	000	3	8/2/2023	NON-COMPETING CONTINUATION	$2,019,244
														Subtotal = $2,019,244

Issue Date FY: 2022 ( Subtotal = $2,029,016 )
2022	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Biology Research	000	2	8/4/2022	NON-COMPETING CONTINUATION	$2,029,016
														Subtotal = $2,029,016

Issue Date FY: 2021 ( Subtotal = $2,060,040 )
2021	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Biology Research	000	1	6/25/2021	NEW	$2,060,040
														Subtotal = $2,060,040

Grand Total All Awards = $10,093,168

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Identifying Metabolic Vulnerabilities in Lung Cancer

Award Number: P01CA250984

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/25/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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