# Targeting EGFR mutant tyrosine kinase inhibitors (TKIs) resistant and drug-tolerant persister cells in non-small cell lung cancer (NSCLC)

> **NIH NIH R50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $140,341

## Abstract

Project Abstract/Summary
The identification of targetable driver oncogenes, such as EGFR, has been a revolutionary
advance in the treatment of lung cancer and other malignancies. In tumors with such genetic
drivers, the vast majority of cells are dependent on specific oncogenes for survival (commonly
referred to as oncogene “addicted” or oncogene-dependent). Effective inhibitors can dramatically
improve clinical outcomes for patients but most of the times these drugs do not completely
eradicate tumors leaving residual cells that are not killed by the initial treatment. These cells,
termed drug-tolerant persister cells (DTPCs), may remain quiescent or clinically invisible for
prolonged periods of time and eventually progress to become resistant cells with enhanced
metastatic potential. My laboratory research efforts over the past decade have been focused, in
large part, on elucidating mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) and
developing strategies to overcome resistance, efforts that have been translated into new drugs
and combinations into the clinic (e.g. poziotinib, Axl+EGFR inhibitors, VEGF+EGFR inhibitors,
etc). Dr. Monique Nilsson has been leading some of these studies including the identification of
stress hormones and IL-6 as drivers of EGFR TKI resistance and the characterization of the
YAP/FOXM1 axis as a critical pathway in the development of EGFR TKI resistance. She also
identified novel targets for EGFR mutant TKI resistant tumors such as aurora kinases. More
recently she was able to demonstrate pre-clinically the mechanisms underlying the VEGF
dependency of EGFR mutant lung tumors. Importantly, Dr. Nilsson’s studies led to several new
clinical trials that are currently ongoing in our institution. In order to prevent the emergence of
drug resistance of EGFR mutant tumors, Dr. Nilsson’s goal in this proposal is to identify novel
treatment strategies to eliminate DTPCs in the early stages. There is little known about the
signaling pathways and potential therapeutic vulnerabilities of DTPCs and we aimed to perform a
deep analysis at the single cell level of a large collection of preclinical models that my laboratory
and Dr. Nilsson have developed during the past years. We believe that these studies will also
help to advance in the understanding of other molecularly defined oncogene-driven lung subtypes
and other solid tumors.

## Key facts

- **NIH application ID:** 10322233
- **Project number:** 1R50CA265307-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Monique B Nilsson
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $140,341
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322233

## Citation

> US National Institutes of Health, RePORTER application 10322233, Targeting EGFR mutant tyrosine kinase inhibitors (TKIs) resistant and drug-tolerant persister cells in non-small cell lung cancer (NSCLC) (1R50CA265307-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322233. Licensed CC0.

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