# Transcriptional Regulation of Lung Cancer Identity

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $18,910

## Abstract

Project Summary
Lung adenocarcinoma, the most common cause of cancer death worldwide, exhibits substantial heterogeneity
in cellular identity, or differentiation state. In this disease, cancer cell identity correlates with critical clinical
parameters, including patient prognosis, intrinsic sensitivity to therapy, and acquisition of drug resistance.
Despite these correlations, major unanswered questions remain with respect to a) the regulatory networks
controlling lung adenocarcinoma identity and (b) the mechanisms by which perturbation of these networks alters
malignant potential. A major rationale for this proposal is that a mechanistic understanding of lineage
specification in lung cancer must be achieved before differentiation state-specific therapeutic strategies can be
developed. The immediate goal of this application is to test the central hypothesis that the transcription factors
NKX2-1/TTF1, FOXA1 and FOXA2 coordinately regulate a gene network that controls lung adenocarcinoma
differentiation and growth. This hypothesis will be tested in the following specific aims via an integrative
experimental approach that employs genetically engineered mouse (GEM) models, analysis of primary human
tumors, and functional studies in human cancer cell lines: (1) Characterize the role of FOXA1 and FOXA2
(FOXA1/2) in NKX2-1-positive lung adenocarcinoma. (2) Determine how global re-localization of FOXA1/2 after
NKX2-1 loss impacts lung adenocarcinoma growth and differentiation. (3) Identify mechanisms by which NKX2-
1 represses non-pulmonary cell fates in lung adenocarcinoma.

## Key facts

- **NIH application ID:** 10330897
- **Project number:** 3R01CA212415-04S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Eric Lee Snyder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $18,910
- **Award type:** 3
- **Project period:** 2017-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330897

## Citation

> US National Institutes of Health, RePORTER application 10330897, Transcriptional Regulation of Lung Cancer Identity (3R01CA212415-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10330897. Licensed CC0.

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