The fundamental role of liquid biopsy in lung cancer: a shift in paradigm in the realm of thoracic oncology

Abstract Lung cancer remains the leading cause of global cancer mortality, with effective management hinging on timely molecular characterization and continuous disease monitoring. Although tissue biopsy continues to be the gold standard for histopathological diagnosis and genomic profiling, its invasive nature, procedural risks, and inability to fully capture spatial and temporal tumor heterogeneity present significant limitations. Liquid biopsy has emerged as a transformative adjunct, offering a minimally invasive, real-time, and dynamic approach to interrogating tumor biology. By analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles (EVs), and other tumor-derived analytes in blood and body fluids, liquid biopsy provides complementary molecular insights that can augment and, in some clinical settings, partially substitute tissue-based testing. In lung cancer, ctDNA has demonstrated strong clinical utility in detecting actionable driver alterations, uncovering resistance mechanisms, guiding targeted therapy sequencing, and monitoring minimal residual disease. CTCs and EVs further contribute to phenotypic and molecular characterization, enabling early detection, prognostication, and evaluation of therapeutic response. As evidence accumulates from multiple large-scale trials, liquid biopsy is reshaping the paradigm of thoracic oncology, supporting more adaptive, personalized, and longitudinal cancer care. While not a replacement for tissue biopsy, its integration into routine practice represents a pivotal advance in precision oncology for lung cancer.