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

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2020 · $416,907

## Abstract

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.

## Key facts

- **NIH application ID:** 9956058
- **Project number:** 1R01CA239093-01A1
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** Sharon R. Pine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $416,907
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956058

## Citation

> US National Institutes of Health, RePORTER application 9956058, Discovery and therapeutic targeting of biological determinants of lung cancer health disparities (1R01CA239093-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9956058. Licensed CC0.

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