Integrating liquid biopsies in non-small cell lung cancer diagnosis and management: opportunities and challenges

Introduction: Liquid biopsy has emerged as an important approach to capture tumor-derived material from blood and other body fluids, offering a minimally invasive window into cancer biology. In non–small cell lung cancer (NSCLC), it enables comprehensive molecular profiling that informs patient management, from guiding therapy choices to monitoring disease status and assessing minimal residual disease (MRD). Areas covered: Its main advantages over tissue biopsy lie in being noninvasive, capable of reflecting tumor heterogeneity and real-time biological changes. These strengths allow liquid biopsy to be applied at different clinical timepoints, including diagnosis, treatment decision-making, evaluation during therapy, detection of resistance, and surveillance for recurrence. Although circulating tumor DNA (ctDNA) remains the most established analyte, the scope is broadening to include circulating RNAs, circulating tumor cells, exosomes, DNA methylation signatures, and tumor-educated platelets, each providing complementary insights. A literature search of PubMed, EMBASE, and Web of Science was conducted without restrictions, supplemented by screening reference lists and major oncology conference abstracts. Expert opinion: While significant progress has been made integrating liquid biopsies in NSCLC, challenges persist, encompassing issues of standardization, cost, and clinical integration.