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Discovery and therapeutic targeting of biological determinants of lung cancer health disparities

Award Number: R01CA239093
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Discovery and therapeutic targeting of biological determinants of lung cancer health disparities - Lung cancer is the leading cause of all cancer deaths in the U.S. and worldwide. Lung cancer risk and survival are heterogeneously distributed among U.S. populations. African-American men have a higher incidence of and poorer survival from lung cancer than European-American men, even after adjusting for smoking and socioeconomic factors. The tumor-specific biological factors responsible for the racial differences are not yet understood. The goal of this project is to define the mechanisms by which the JAK/STAT3 pathway operates as a key biological contributor of racial health disparities in non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), the most common histological subtype of lung cancer. Our preliminary data suggest that LUADs from African Americans are more likely than LUADs from European Americans to have JAK/STAT3 pathway mutations that directly induce persistent activation of Signal Transducer and Activator of Transcription-3 (STAT3). STAT3 is an oncogenic transcription factor that is hyperactivated in many cancers. It drives expression of genes that regulate anti-apoptotic responses, angiogenesis, cell proliferation, tumor progression, and therapeutic resistance. The premise of this application is that the JAK/STAT3 signaling axis is inappropriately activated by mutations that are more common in LUAD from African Americans than European Americans, and that therapeutic intervention will be of clinical benefit to a molecular subset of patients with LUAD. Given that the molecular subset is more common in African Americans, research on this topic could help narrow the gap in health disparities. Aim 1 will characterize the molecular profiles in LUAD from African Americans and European Americans focusing on JAK/STAT3 and impact on racial differences. In Aim 2, we will utilize CRISPR-mediated genome editing on patient-derived models of cancer from LUAD tumors from African Americans, and other models, to test the hypothesis that aberrant STAT3 activation results from specific mutations in the JAK/STAT3 pathway, and that the mutations drive LUAD development and tumor progression. In Aim 3, utilizing patient-derived LUAD xenografts primarily from African-American patients, we will test the hypothesis that the JAK/STAT3 pathway mutations we identified can serve as predictive biomarkers for effective antitumor response to STAT3 blockade in LUAD, and we will further clarify novel biomarkers of effective tumor response. At the conclusion of this project, we will have uncovered a novel set of biological determinants of NSCLC health disparities. If the results of the study support our hypothesis, they will provide a path to future clinical trials that may improve the clinical outcome of LUAD patients and help reduce lung cancer health disparities.


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 = $433,114 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	6	2/14/2025	NON-COMPETING CONTINUATION	$389,804
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	6	5/23/2025	NON-COMPETING CONTINUATION	$43,310
														Subtotal = $433,114

Issue Date FY: 2024 ( Subtotal = $441,169 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	5	4/24/2024	NON-COMPETING CONTINUATION	$23,219
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	000	5	1/29/2024	NON-COMPETING CONTINUATION	$417,950
														Subtotal = $441,169

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	004	3	6/12/2023	NON-COMPETING CONTINUATION	-$50,677
2023	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	001	4	3/16/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$373,775
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	3	3/16/2023	NON-COMPETING CONTINUATION	-$373,775
2023	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	005	4	6/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$73,957
2023	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Cancer Biology Research	002	4	6/8/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2023	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	003	2	6/12/2023	NON-COMPETING CONTINUATION	-$23,280
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $424,452 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	3	4/22/2022	NON-COMPETING CONTINUATION	$424,452
														Subtotal = $424,452

Issue Date FY: 2021 ( Subtotal = $430,226 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	2	4/6/2021	NON-COMPETING CONTINUATION	$430,226
														Subtotal = $430,226

Issue Date FY: 2020 ( Subtotal = $416,907 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	195 LITTLE ALBANY ST	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Cancer Biology Research	000	1	5/4/2020	NEW	$416,907
														Subtotal = $416,907

Grand Total All Awards = $2,145,868

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Discovery and therapeutic targeting of biological determinants of lung cancer health disparities

Award Number: R01CA239093

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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