# Evolution of resistance of EGFR mutant non-small cell lung cancer

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $179,280

## Abstract

NIH Mentored Clinical Scientist Research Career Development Award (K08) Application
FOA number: PA-14-046
Project: Evolution of resistance of EGFR mutant non-small cell lung cancer
Applicant: Aaron Hata
Project Summary/Abstract
 Advances in our understanding of the genetic alterations in cancer have given rise to effective therapies
that target specific oncogenic signaling pathways. For instance, treatment of non-small cell lung cancers
(NSCLCs) harboring activating mutations in the epidermal growth factor receptor (EGFR) with small molecule
EGFR inhibitors leads to dramatic clinical responses. Unfortunately, the clinical effectiveness of targeted
therapies is limited by the inevitable emergence of acquired drug resistance that ultimately renders the therapy
ineffective. Understanding these mechanisms of resistance is fundamental to developing improved treatment
strategies to improve patient outcomes.
 In this project, Dr. Hata proposes to study the evolution of acquired resistance of EGFR mutant NSCLC. Dr.
Hata is an Instructor in Medicine at Harvard Medical School and a member of the Hematology/Oncology faculty
at the Massachusetts General Hospital Cancer Center. As a Hematology/Oncology Fellow in the Dana
Farber/Partners CancerCare Oncology Training program, Dr. Hata joined the laboratory of Dr. Jeffrey
Engelman in the MGH Center for Cancer Research in 2010, where he has focused on understanding how
changes in apoptotic signaling affect sensitivity and resistance to targeted therapies. Since joining the MGH
faculty in 2013, Dr. Hata has continued his research studies in the Engelman Laboratory, and is now interested
in applying insights gained from his prior work toward understanding how EGFR mutant NSCLC resistant
clones emerge and evolve during therapy.
 Dr. Hata recently demonstrated that genetic mechanisms of resistance such as the EGFRT790M mutation
can evolve de novo from surviving drug tolerant cells during drug treatment, suggesting that drug tolerant cells
that do not yet harbor genetic mechanisms of resistance can serve as an important reservoir for subsequent
evolution of resistance. In this project, Dr. Hata proposes to investigate the evolution of acquired resistance of
EGFR mutant NSCLC to EGFR inhibitors in patients. Examining tumor biopsy specimens from patients at the
time of disease progression for genetic signatures that accumulate in drug tolerant cells, he will determine
whether resistant cancers derived from pre-existing resistant sub-clones or evolved during therapy. He will
integrate analysis of tumor cells from patients undergoing EGFR inhibitor therapy with functional studies using
laboratory tumor models derived from these same patients to characterize drug tolerant tumor cells in vivo.
Finally, he will investigate novel drug treatment strategies designed to target drug tolerant cells in vivo. These
studies will significantly enhance our understanding of how acquired drug resistance evolves in the clinic and
identify...

## Key facts

- **NIH application ID:** 9994846
- **Project number:** 5K08CA197389-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Aaron N Hata
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $179,280
- **Award type:** 5
- **Project period:** 2016-09-14 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994846

## Citation

> US National Institutes of Health, RePORTER application 9994846, Evolution of resistance of EGFR mutant non-small cell lung cancer (5K08CA197389-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9994846. Licensed CC0.

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