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Updated: Jul 14, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity

Haris Vikis1, Mitsuo Sato, Michael James

  • 1Washington University, St. Louis, Missouri, USA.

Cancer Research
|May 19, 2007
PubMed

Insights

The T790M mutation in epidermal growth factor receptor (EGFR) enhances its kinase activity, promoting cell proliferation. This finding suggests EGFR-T790M may rarely contribute to inherited lung cancer susceptibility.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tyrosine kinase inhibitors (TKIs) are effective for lung adenocarcinoma but resistance often develops.
  • Acquired resistance is frequently linked to the T790M mutation in the epidermal growth factor receptor (EGFR).
  • A prior report suggested EGFR-T790M as a germline mutation associated with inherited lung cancer risk.

Purpose of the Study:

  • To investigate the functional impact of the EGFR-T790M mutation.
  • To determine if EGFR-T790M is associated with inherited susceptibility to lung cancer.

Main Methods:

  • Analysis of EGFR-T790M phosphorylation levels.
  • Overexpression of EGFR-T790M in a human bronchial epithelial cell line.
  • Screening of lung cancer family probands and bronchoalveolar tumors for the EGFR-T790M mutation.

Main Results:

  • The T790M mutation increases EGFR phosphorylation at Y992 and Y1068.
  • EGFR-T790M overexpression confers a growth advantage over wild-type EGFR.
  • The EGFR-T790M mutation was not detected in screened lung cancer families or tumors.

Conclusions:

  • EGFR-T790M exhibits enhanced kinase activity and promotes cell proliferation.
  • The study contradicts previous findings regarding EGFR-T790M as a common germline mutation.
  • EGFR-T790M's proliferative advantage suggests a potential role in rare instances of inherited lung cancer risk.

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