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Updated: May 8, 2026

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
07:59

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

Genetics and biomarkers in personalisation of lung cancer treatment

Rafael Rosell1, Trever G Bivona, Niki Karachaliou

  • 1Catalan Institute of Oncology Badalona, Spain. rrosell@iconcologia.net

Lancet (London, England)
|August 27, 2013
PubMed

Insights

Targeted therapies for non-small cell lung cancer (NSCLC) show promise but are often short-lived. Understanding resistance mechanisms, like EGFR Thr790Met mutations and AXL overexpression, is key to developing effective combination treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small-cell lung cancer (NSCLC) frequently presents at the metastatic stage, with a median survival of only one year.
  • Epidermal growth factor receptor (EGFR) driver mutations are key oncogenic events in a subset of lung adenocarcinomas, enabling targeted therapy.
  • EGFR tyrosine kinase inhibitors (TKIs) induce remission in approximately 60% of patients, but responses are often transient.

Purpose of the Study:

  • To investigate mechanisms of resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small-cell lung cancer.
  • To identify novel biomarkers and potential combination therapies for overcoming treatment resistance.

Main Methods:

  • Analysis of pre-existing EGFR Thr790Met mutations as a potential driver of transient responses.
  • Investigation of AXL overexpression and MED12 function as hallmarks of TKI resistance.
  • Exploration of signaling pathway crosstalk as a resistance mechanism.

Main Results:

  • The EGFR Thr790Met mutation may contribute to short-lived responses to TKIs.
  • Overexpression of AXL and reduced MED12 function are associated with resistance to TKIs in EGFR-mutant NSCLC.
  • Signaling pathway crosstalk represents another significant mechanism of resistance.

Conclusions:

  • Identification of molecular components involved in resistance pathways can guide the development of combination therapies.
  • Cotargeting multiple molecules, rather than EGFR TKI monotherapy, may improve treatment outcomes.
  • Deep sequencing of serial rebiopsies holds potential for identifying novel biomarkers.

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