NTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types

Summary: This study reveals that TRK xDFG mutations in TRK fusion-positive cancers confer resistance to type I TRK inhibitors but may serve as a potential biomarker for the activity of type II TRK inhibitors, which should be the focus of rational drug design.

Summary: Although precision medicine has had mixed impact on clinical management of patients with advanced-stage cancer overall, the advances have been dramatic for NSCLC, specifically lung adenocarcinoma, due to genomic complexity and increasing number of druggable oncogene drivers. Liquid biopsy serves as a practical alternative source for investigating tumor-derived somatic alterations, offering a minimally invasive approach for selecting targeted therapies. The most extensively studied methodology is plasma circulating tumor DNA, which has wide adoption as an alternative to tissue tumor genotyping, particularly in solid tumors like NSCLC.