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Updated: Jan 31, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

413

Emerging drugs for EGFR-mutated non-small cell lung cancer

Vineeth Sukrithan1, Lei Deng2, Alexander Barbaro3

  • 1a Department of Oncology , Montefiore Medical Center/Albert Einstein College of Medicine , Bronx , NY , USA.

Expert Opinion on Emerging Drugs
|December 21, 2018
PubMed
Abstract

Insights

Newer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) show promise for non-small-cell lung cancer (NSCLC) patients with EGFR mutations, despite inevitable resistance. Understanding resistance mechanisms is key to developing future therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard for metastatic non-small-cell lung cancer (NSCLC) with EGFR mutations.
  • Treatment resistance is an inevitable challenge with current EGFR TKIs.
  • Newer generations of TKIs aim to overcome resistance and improve efficacy, including in the brain.

Purpose of the Study:

  • To review newer generations of EGFR TKIs for EGFR-mutated NSCLC.
  • To discuss resistance mutations and escape pathways associated with EGFR TKIs.
  • To cover emerging data from combination trials with next-generation TKIs.

Main Methods:

  • Literature review of newer EGFR TKIs.
  • Analysis of resistance mechanisms (secondary mutations, bypass pathways, etc.).
  • Review of combination therapy trials.

Main Results:

  • Third-generation TKIs demonstrate superior efficacy in the front-line setting and are now standard of care.
  • Various resistance mechanisms and escape pathways have been identified.
  • Combination trials are exploring strategies to delay or prevent resistance.

Conclusions:

  • Third-generation EGFR TKIs have become standard for EGFR-mutated NSCLC due to superior efficacy.
  • Further understanding of treatment failure mechanisms is crucial for future therapeutic advancements.
  • Developing novel strategies is essential to improve patient outcomes by overcoming resistance and relapse.
Keywords:
EGFRNSCLCresistance mechanismstyrosine kinase inhibitors

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