# Intercepting progression from pre-invasive to invasive lung adenocarcinoma

> **NIH NIH UG3** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $130,578

## Abstract

Abstract
Despite advances in therapeutic strategies, non-small cell lung cancer remains a deadly disease. An
improved understanding of the biology of lung cancer is needed to intercept the disease at an early point in
its progression. Our project, which is inspired by that challenge, focuses on events transpiring in the earliest
radiographically-detected manifestation of lung cancer: the computerized tomography (CT)-detected non-
solid nodule, of which as many as 40% harbor frankly invasive adenocarcinoma. Thus, despite conventional
wisdom that CT-detected non-solid nodules represent pre or minimally invasive malignancy, clearly transition
to more invasive histologies occurs in a significant proportion of these nodules.
Understanding the cellular and molecular changes within non-solid nodules that drive progression will provide
unique and novel insights into the fundamental mechanisms of lung carcinogenesis. We hypothesize that
alterations in cells of the tumor microenvironment (TME) have a role in initiating and supporting this
progression. In agreement with that proposal, our preliminary multiplex immunofluorescence (IF) studies
suggest that progression to a more invasive phenotype is associated with the development of a strong
immunosuppressive TME. In this project we test our hypothesis using multidimensional methods to profile the
TME and to determine the crosstalk between cancer cells and the TME in pre-invasive to invasive human
lung non-solid adenocarcinomas. Comparative analysis of the cellular and molecular events associated with
the distinct histological stages will lead to identification of the critical events triggering progression and
thereby identify targets to intercept disease progression. We will use appropriate mouse models in pre-clinical
studies to develop these targets as strategies to intercept progression of pre-invasive to invasive cancer.
In the first phase of these studies (UG3 phase), we will define TME alterations associated with progression of
lung nodules using RNAseq profiling and image-based methods (multiplex IF and imaging CyTOF) in studies
of our archival tumor samples. These studies will generate a comprehensive catalogue of the cellular and
molecular events that trigger progression of indolent lesions to frankly invasive cancers, with a strong focus
on immune mechanisms. These analyses will provide novel and detailed insights into how the composition
and activity of the TME changes with progression. In the second phase (UH3 phase), we will leverage mouse
models to explore interception strategies to target immune mechanisms and prevent progression.
The proposed cohort satisfies the RFA’s focus on High-Risk Cohorts for Cancer-Immunoprevention Studies,
since lung nodules are premalignancies highly prevalent in smokers.

## Key facts

- **NIH application ID:** 10117907
- **Project number:** 3UG3CA244697-02S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** NASSER Khaled ALTORKI
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $130,578
- **Award type:** 3
- **Project period:** 2019-09-25 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117907

## Citation

> US National Institutes of Health, RePORTER application 10117907, Intercepting progression from pre-invasive to invasive lung adenocarcinoma (3UG3CA244697-02S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10117907. Licensed CC0.

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