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Updated: Jul 4, 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 Dysregulation in Cancer: From Molecular Mechanisms and Key Mutations to Evolving TKI Strategies and Resistance

Amna Tamimi1, Mantasha Khan1, Mohammad Kalim Ahmad Khan1

  • 1Department of Bioengineering, Integral University, Lucknow, India.

Current Medicinal Chemistry
|July 3, 2026
PubMed
Abstract

Insights

Epidermal growth factor receptor (EGFR) dysregulation drives cancer, especially non-small cell lung cancer. New therapies and precision oncology offer hope for overcoming resistance and improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) signaling is crucial for cell growth, survival, and differentiation.
  • EGFR dysregulation, through overexpression or mutations, is a key driver in various cancers, notably non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To provide a comprehensive review of EGFR biology, its associated signaling pathways, and current therapeutic targeting strategies.
  • To explore the evolution of EGFR-targeted therapies from early inhibitors to novel approaches like fourth-generation TKIs, PROTACs, and combination immunotherapies.

Main Methods:

  • Literature review synthesizing research on EGFR structure, ligand interactions, and downstream signaling pathways (RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, JAK/STAT, PLCγ/PKC).
  • Analysis of resistance mechanisms, including triple mutant EGFR (L858R, T790M, C797S), and the development of targeted inhibitors.
  • Examination of emerging treatment strategies such as fourth-generation TKIs, allosteric inhibitors, PROTACs, combination immunotherapy, and precision medicine.

Main Results:

  • EGFR-targeted treatments have significantly improved outcomes for NSCLC patients with activating mutations.
  • Therapeutic effectiveness is often limited by resistance mechanisms, particularly secondary mutations.
  • Ongoing research into novel treatment strategies shows promise for overcoming resistance and enhancing treatment efficacy.

Conclusions:

  • Understanding EGFR at a molecular level combined with advanced therapeutic strategies underscores the importance of precision oncology in cancer treatment.
  • Further research into the interplay between signaling pathways, mutations, and drug responses is essential for optimizing treatment outcomes.
  • This review highlights current knowledge and future directions in EGFR-targeted therapy, emphasizing newer strategies and the role of precision oncology.
Keywords:
C797SEpidermal growth factor receptorErbB1L858RNSCLCT790Mtyrosine kinase inhibitors

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