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Updated: Sep 26, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
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Acquired Mechanisms of Resistance to Osimertinib-The Next Challenge

Alejandro Ríos-Hoyo1, Laura Moliner1, Edurne Arriola1,2

  • 1Department of Medical Oncology, Hospital del Mar-CIBERONC (Centro de Investigación Biomédica en Red de Oncología), 08003 Barcelona, Spain.

Cancers
|April 23, 2022
PubMed

Insights

Epidermal growth factor receptor (EGFR) mutations drive non-small cell lung cancer. While osimertinib is effective, resistance develops, limiting treatment options for EGFR-mutated lung cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancer (NSCLC).
  • Osimertinib offers significant clinical benefit for EGFR-mutated NSCLC but acquired resistance is inevitable.
  • Limited effective treatment options exist for patients progressing on osimertinib.

Purpose of the Study:

  • To review common resistance mechanisms to osimertinib in EGFR-mutated NSCLC.
  • To discuss emerging therapeutic strategies to overcome these resistance mechanisms.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of identified resistance alterations and treatment outcomes.

Main Results:

  • Multiple genetic and non-genetic mechanisms of resistance to osimertinib have been identified.
  • Specific alterations, such as C797S mutations and MET amplification, are frequently observed.
  • Investigational therapies targeting these resistance mechanisms are under development.

Conclusions:

  • Understanding resistance mechanisms is crucial for managing EGFR-mutated NSCLC.
  • Novel therapeutic strategies show promise in overcoming osimertinib resistance.
  • Personalized treatment approaches are needed for patients with acquired resistance.
Keywords:
EGFRNSCLCmechanisms of resistanceosimertinib

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