# Inhibitor-sensitive and -resistant EGFR mutants from lung cancer and glioblastoma

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2020 · $374,063

## Abstract

Project Summary
 The epidermal growth factor receptor (EGFR) tyrosine kinase is one of the most commonly activated
oncoproteins in lung adenocarcinoma, glioblastoma and other cancers. The identification of cancer-associated
EGFR mutants and their predictive power to select patients for treatment with EGFR inhibitors constitutes a
major advance in treatment of these cancers. The collaborative efforts of the Eck and Meyerson laboratories
over the past 12 years have provided a detailed structural and mechanistic understanding of selected
activating and resistance mutations in EGFR, and have led to new classes of inhibitors that can overcome
treatment-acquired resistance. In this renewal, we propose to perform studies that will inform the discovery of
inhibitors of EGFR variants for which current treatments are ineffective, including exon20 insertion mutants in
non-small cell lung cancer and EGFRvIII mutants in glioblastoma. In addition, we propose to probe the
structure and regulation of the intact receptor to better understand its oncogenic activation. We will undertake
the following Specific Aims: Aim 1) Analyze the biochemical and structural impact of small-molecule kinase
inhibitors on EGFR exon20 insertion mutants, Aim 2) Develop allosteric inhibitors that selectively inhibit the
EGFRvIII variant in glioblastoma, and Aim 3) Structure elucidation of the complete EGF receptor. Execution of
these aims will lead to small molecules that will serve as templates for next-generation therapeutics for EGFR-
driven cancers that do not respond to current EGFR targeted agents. Additionally, our structural and
biochemical studies will illuminate mechanisms of receptor activation and signaling in both normal and
oncogenic contexts that may suggest new avenues for therapeutic intervention in the future.

## Key facts

- **NIH application ID:** 9895628
- **Project number:** 5R01CA116020-14
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** MICHAEL J ECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,063
- **Award type:** 5
- **Project period:** 2006-03-24 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895628

## Citation

> US National Institutes of Health, RePORTER application 9895628, Inhibitor-sensitive and -resistant EGFR mutants from lung cancer and glioblastoma (5R01CA116020-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9895628. Licensed CC0.

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