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.

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.