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 nextgeneration 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.