Acquired Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers: The Role of Next-Generation Sequencing on Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Samples

Arch Pathol Lab Med. 2018 Apr;142(4):465-473. doi: 10.5858/arpa.2017-0158-RA.


Context: - Molecular testing is essential for the diagnostic workup of patients with advanced non-small cell lung cancers. Cytology specimens from minimally invasive procedures, such as endobronchial ultrasound-guided transbronchial needle aspiration, are often the only available samples for these patients. The implementation of molecular diagnostic testing, and in particular next-generation sequencing-based testing, on these cytologic specimens is currently an evolving field for lung cytopathology. The application of these molecular analyses on tyrosine kinase inhibitor-resistant non-small cell lung cancers raises unique technical, biologic, and clinical challenges.

Objective: - To provide an overview of the implementation of next-generation sequencing analysis on endobronchial ultrasound-guided transbronchial needle aspiration samples to detect the molecular aberrations underneath the phenomenon of acquired resistance in patients with non-small cell lung cancers progressing while on the EGFR/ALK tyrosine kinase inhibitor treatment.

Data sources: - Peer-reviewed original articles, review articles, and published guidelines and expert opinion reports were reviewed, together with our single-center experience.

Conclusions: - Next-generation sequencing analyses and the endobronchial ultrasound-guided transbronchial needle aspiration procedure may represent a valuable strategy to address the unique requirements of molecular testing on tyrosine kinase inhibitor-resistant non-small cell lung cancers.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Drug Resistance, Neoplasm*
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / diagnosis*
  • Male
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors


  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases