Liquid biopsy application has gained rising attention in oncology fields, especially for circulating tumor DNA (ctDNA) in clinical utility. Based on a presentation from the International Association for the Study of Lung Cancer (IASLC) Annual Conference in Japan, the researchers recruited 76 advanced non-small cell lung cancer (NSCLC) patients with unknown driver mutations and adopted next-generation sequencing (NGS) with a 21 gene assay to identify unknown drivers in ctDNA. The results showed that detection rate is 60% of patients. Moreover, oncogenic drivers were detected, including HER2 exon 20 insYVMA, BRAF L597Q and MET exon 14 mutations in 27 patients (36%). Among patients with oncogenic mutations, 11 (14%) patients were enrolled in clinical trials, and 10 patients showed partial response after genotype-matched therapies. These findings suggest that via NGS, liquid biopsy can be utilized to detect driver mutations and guide further treatment in clinical setting in the future.