# Transcriptional Regulation of Lung Cancer Identity

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $316,438

## 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:** 9961501
- **Project number:** 5R01CA212415-04
- **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:** 2020
- **Award amount:** $316,438
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961501

## Citation

> US National Institutes of Health, RePORTER application 9961501, Transcriptional Regulation of Lung Cancer Identity (5R01CA212415-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961501. Licensed CC0.

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