Grant Number:	5R01CA256724-04 Interpret this number
Primary Investigator:	Singh, Shailesh
Organization:	Morehouse School Of Medicine
Project Title:	The Interplay of Social and Molecular Determinants in Lung Cancer Disparity
Fiscal Year:	2026

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.




Revolutionizing Oncology Through AI: Addressing Cancer Disparities by Improving Screening, Treatment, and Survival Outcomes via Integration of Social Determinants of Health.
Authors: Srivastav A.K. , Singh A. , Singh S. , Rivers B. , Lillard J.W. , Singh R. .
Source: Cancers, 2025-08-31 00:00:00.0; 17(17), .
EPub date: 2025-08-31 00:00:00.0.
PMID: 40940963
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Elevated CCL20 and IL-10 enhance 5-fluorouracil tolerance in colon cancer.
Authors: Muralidharan J. , Eswaran M. , Bae S. , Singh S. , Mir H. .
Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 2025 Aug; 189, p. 118258.
EPub date: 2025-06-21 00:00:00.0.
PMID: 40544749
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Transforming Pharmacogenomics and CRISPR Gene Editing with the Power of Artificial Intelligence for Precision Medicine.
Authors: Srivastav A.K. , Mishra M.K. , Lillard J.W. , Singh R. .
Source: Pharmaceutics, 2025-04-24 00:00:00.0; 17(5), .
EPub date: 2025-04-24 00:00:00.0.
PMID: 40430848
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Nanotechnology for boosting ovarian cancer immunotherapy.
Authors: Kaur P. , Singh S.K. , Mishra M.K. , Singh S. , Singh R. .
Source: Journal Of Ovarian Research, 2024-10-14 00:00:00.0; 17(1), p. 202.
EPub date: 2024-10-14 00:00:00.0.
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Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer.
Authors: Kaur P. , Singh S.K. , Mishra M.K. , Singh S. , Singh R. .
Source: Cancers, 2024-06-12 00:00:00.0; 16(12), .
EPub date: 2024-06-12 00:00:00.0.
PMID: 38927911
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Emerging Trends in Nanotechnology for Endometriosis: Diagnosis to Therapy.
Authors: Talukdar S. , Singh S.K. , Mishra M.K. , Singh R. .
Source: Nanomaterials (basel, Switzerland), 2024-06-05 00:00:00.0; 14(11), .
EPub date: 2024-06-05 00:00:00.0.
PMID: 38869601
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Social and Biological Determinants in Lung Cancer Disparity.
Authors: Brock B.A. , Mir H. , Flenaugh E.L. , Oprea-Ilies G. , Singh R. , Singh S. .
Source: Cancers, 2024-01-31 00:00:00.0; 16(3), .
EPub date: 2024-01-31 00:00:00.0.
PMID: 38339362
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The effect of paclitaxel- and fisetin-loaded PBM nanoparticles on apoptosis and reversal of drug resistance gene ABCG2 in ovarian cancer.
Authors: McFadden M. , Singh S.K. , Kinnel B. , Varambally S. , Singh R. .
Source: Journal Of Ovarian Research, 2023-11-21 00:00:00.0; 16(1), p. 220.
EPub date: 2023-11-21 00:00:00.0.
PMID: 37990267
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Targeted Therapy and Mechanisms of Drug Resistance in Breast Cancer.
Authors: Kinnel B. , Singh S.K. , Oprea-Ilies G. , Singh R. .
Source: Cancers, 2023-02-19 00:00:00.0; 15(4), .
EPub date: 2023-02-19 00:00:00.0.
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