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Precision medicine based on the driver genes mutation status is the current systemic therapeutic paradigm in patients with lung cancer. Next-generation sequencing (NGS) has emerged as a powerful platform for molecular diagnosis by virtue of high-throughput and massively parallel sequencing. Liquid biopsy also enabled the dynamic monitoring and comprehensive profiling of lung cancer in a noninvasive manner. However, challenges remain in the field of technology and clinical applications, especially in the era of immunotherapy. Here, we update the role of NGS in the context of lung cancer screening, molecular diagnosis, predictive and prognostic biomarkers, and guiding personalized treatment. The NGS application for actable genomic alternation has greatly changed the therapeutic landscape in patients with lung cancer including perioperative setting and advanced stage. Meanwhile, emerging evidence has shown the potential of other applications such as early screening and detection, and MRD. However, challenges remain such as the lack of standardized protocols across different platforms and bioinformatics analysis pipelines, and the complexity of interpreting and leveraging numerous genomic mutation messages for therapy selection. Future research is needed to overcome these challenges and expand the applications of NGS to other aspects such as immunotherapy.

Recent advance of next-generation sequencing in patients with lung cancer