# Studying the initiation, progression and therapy of lung cancer in mouse models

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $365,750

## Abstract

PROJECT ABSTRACT
 Lung cancer is a global scourge responsible for ~1.5 million deaths worldwide, and ~130,000 deaths in the
USA in 2022. Despite our understanding of relevant risk factors such as cigarettes, asbestos and radon, lung
cancer kills more US citizens than the next four cancer types combined. Although the clinical situation is
challenging, fundamental cancer research has revealed that lung cancers can be subdivided into genetically-
defined subsets based on driver oncogene mutations that, in turn, serve as predictive biomarkers for the clinical
deployment of FDA-approved pathway-targeted therapies in lung cancer patients. In particular, FDA approval
of oncoprotein-targeted therapies such sotorasib or dabrafenib plus trametinib as treatments for KRASG12C or
BRAFV600E-driven lung cancer respectively are already having an important impact on patients with these subsets
of the disease. However, despite this, and recent advances in the deployment of immunotherapy, only a minority
of lung cancer patients have benefitted from such advances such that treatment options for many patients remain
limited to conventional approaches including surgery, radiation, and/or conventional chemotherapy that are
ineffective against tumor cells and toxic to the patient. Consequently, the overarching, long-term goal of this
research is to provide a rational scientific foundation for the development of new combination therapeutic
strategies to treat patients with KRAS- or BRAF-driven lung cancer that: 1. Increase the overall response rate
and depth of each patient's primary response; 2. Maximize safety and tolerability, while minimizing toxicity and;
3. Forestall the onset of lethal drug resistance. To that end, our short-term aims are to elucidate how various
signaling pathways cooperate with oncogenic KRAS or BRAF in the genesis and maintenance of lung cancer.
To do so we will leverage: 1. State-of-the-art preclinical mouse models (GEM or PDX) of KRAS- or BRAF-driven
lung cancer; 2. Human or mouse lung cancer-derived cell lines whose aberrant behavior is driven by relevant
genetic abnormalities; 3. Pathway-targeted inhibitors, many of which are FDA-approved or in clinical
development and; 4. An outstanding collaborative team of scientists and physicians who will consult on the
design, execution and interpretation of the results of our research. Hence, building on a solid foundation of
published or preliminary data, we will use models of KRAS- or BRAF-driven lung cancer to elucidate the role of:
1. Autocrine activation of ERBB/HER signaling as a mechanism that promotes lung cancer progression and
maintenance; 2. Autophagy as a cytoprotective mechanism that protects lung cancer cells from the cytotoxic
effects of pathway-targeted inhibition and; 3. AKT protein kinases as progression factors or pharmacological
targets in the genesis or maintenance of lung cancer. Consequently, our research is significant and likely to
have lasting and important translational imp...

## Key facts

- **NIH application ID:** 10755351
- **Project number:** 5R01CA131261-12
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** MARTIN MCMAHON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $365,750
- **Award type:** 5
- **Project period:** 2009-04-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10755351

## Citation

> US National Institutes of Health, RePORTER application 10755351, Studying the initiation, progression and therapy of lung cancer in mouse models (5R01CA131261-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10755351. Licensed CC0.

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