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Updated: Jun 25, 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

Mechanisms of tumor resistance to EGFR-targeted therapies

Elizabeth A Hopper-Borge1, Rochelle E Nasto, Vladimir Ratushny

  • 1Fox Chase Cancer Center, W462, 333 Cottman Ave., Philadelphia, PA 19111, USA.

Expert Opinion on Therapeutic Targets
|February 25, 2009
PubMed
Abstract

Insights

Resistance to epidermal growth factor receptor (EGFR) therapies arises from multiple mechanisms, including transporter activation and EGFR mutations. Understanding these resistance pathways is key to improving cancer treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) is a key target for cancer therapies.
  • EGFR inhibitors show efficacy in specific cancers, often in combination therapies.
  • Intrinsic or acquired resistance limits the clinical effectiveness of EGFR inhibitors.

Purpose of the Study:

  • To comprehensively review cellular mechanisms of resistance to EGFR-targeted therapies.
  • To explore current and future strategies for overcoming resistance.
  • To discuss emerging systems biology concepts in EGFR inhibitor resistance.

Main Methods:

  • Literature review of cellular resistance mechanisms to EGFR inhibitors.
  • Analysis of validated resistance pathways.
  • Discussion of systems biology approaches to resistance.

Main Results:

  • Validated resistance mechanisms include ABC transporter activation, EGFR mutations or activation, and altered signaling proteins.
  • These mechanisms contribute to intrinsic and acquired resistance.
  • Emerging resistance concepts are being identified through systems biology.

Conclusions:

  • Overcoming resistance requires understanding and targeting multiple pathways.
  • Strategies to circumvent resistance are under development.
  • Systems biology offers new insights into complex resistance networks for targeted therapies.

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