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The interplay of social and molecular determinants in lung cancer disparity

Award Number: R01CA256724
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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The interplay of social and molecular determinants in lung cancer disparity - African Americans (AAs) experience a disproportionate burden of lung cancer compared with other racial and ethnic groups, with higher incidence and poor survival. The increased frequency of aggressive disease among AAs highlights an important need for studies that define racial and ethnic differences in lung cancer. Our goal is to address an insufficiently characterized knowledge gap by identifying molecular, biological, and social determinants, including neighborhood-level factors, that contribute to the disease’s aggressiveness and outcome differences between African Americans (AAs) and European Americans (EAs). Our central hypothesis is that CC chemokine receptor-6 (CCR6) and its sole natural ligand, CCL20, contribute to race-associated differences in molecular footprint and immune landscape, thereby contributing to differences in lung cancer aggressiveness and prognosis. In parallel, social stress–related factors associated with elevated cortisol further modify immune regulation in AAs, contributing to variation in tumor behavior and outcomes. The combined influence of CCR6/CCL20 signaling and social characteristics represents a previously under-examined contributor to lung cancer disparities. Hence, the proposed work will advance mechanistic understanding of cellular and immunologic features of aggressive lung cancers, particularly non-small cell lung cancer (NSCLC), which accounts for ~85% of lung cancers and contributes substantially to ethnic disparities in disease outcomes. To accomplish these goals, we have assembled a multidisciplinary research team with complementary expertise in cancer immunobiology, oncology, pulmonary care, pathology, public health/behavioral science, bioinformatics, and biostatistics to investigate the following aims: A1. Establish the association of the CCR6-CCL20 axis in NSCLC aggressiveness and therapeutic response among AAs and EAs; A2. Ascertain the race-specific differences in the immunological landscape contributing to the NSCLC disparity and A 3. Determine the impact of social stress on the immune signature among AA and EA NSCLC patients. Completion of these aims will i) inform a rapid, non-invasive chemokine based detection methods which will allow classifying potentially fatal lung cancers, ii) a method for early patient stratification so that risk-adapted chemokine-based therapies can be designed to match patient subgroups with distinct CCR6 profiles, iii) to offer improved treatment approach, iv) a framework for improving the success rate of clinical trials involving investigational drugs by establishing new criteria for patient classification, Immune-based strategies to reduce disparity and, v) inform components of multifactorial and multilevel cancer control clinical and non-clinical intervention to strengthen anti-tumor immunity to reduce risk and inform efforts related to survival outcomes of lung cancer.


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: 2026 ( Subtotal = $530,368 )
2026	2026	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	000	4	1/26/2026	NON-COMPETING CONTINUATION	$530,368
														Subtotal = $530,368

Issue Date FY: 2025 ( Subtotal = $589,299 )
2025	2025	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	000	3	12/13/2024	NON-COMPETING CONTINUATION	$530,369
2025	2025	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	001	3	6/24/2025	NON-COMPETING CONTINUATION	$58,930
														Subtotal = $589,299

Issue Date FY: 2024 ( Subtotal = $559,834 )
2024	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	001	2	12/28/2023	NON-COMPETING CONTINUATION	$530,370
2024	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	002	2	4/17/2024	NON-COMPETING CONTINUATION	$29,464
2024	2022	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	000	1	10/18/2023	NEW	$0
														Subtotal = $559,834

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	000	1	8/4/2023	NEW	$0
2023	2022	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	001	1	8/18/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $589,297 )
2022	2022	MOREHOUSE SCHOOL OF MEDICINE, INC., THE	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Cancer Cause and Prevention Research	000	1	6/29/2022	NEW	$589,297
														Subtotal = $589,297

Grand Total All Awards = $2,268,798

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The interplay of social and molecular determinants in lung cancer disparity

Award Number: R01CA256724

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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