Cancer in a drop: Liquid biopsy highlights from the World Conference on Lung Cancer (WCLC) 2025

The role of liquid biopsy in oncological care continues to expand, with multiple studies presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC 2025). This review summarizes recent advances in liquid biopsy for thoracic oncology, encompassing both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In early detection and screening, proteomic profiling has identified potential biomarkers predictive of future lung cancer risk. The integration of proteomics with clinical and imaging data can improve pulmonary nodule malignancy prediction. In resectable NSCLC, tumour-informed whole-genome sequencing (WGS) assay demonstrated high sensitivity for minimal residual disease (MRD) detection, with MRD clearance following neoadjuvant osimertinib or chemo-immunotherapy associated with favorable outcomes. In advanced NSCLC, longitudinal liquid biopsy analyses reveal dynamic subclonal evolution driving early treatment resistance. Circulating tumor DNA (ctDNA) clearance following targeted therapy in MET exon 14 skipping and BRAF-mutated tumors was associated with improved clinical outcomes. Emerging biomarkers such as ctDNA tumour fraction and circulating microRNA signatures are promising for radiotherapy stratification and prediction of immunotherapy-related toxicities. In SCLC, MRD monitoring enables earlier detection of disease progression and supports ctDNA-guided selection of patients for consolidation immunotherapy following chemotherapy. Overall, these advances demonstrate the expanding role of liquid biopsy in improving early detection, guiding treatment, and improving disease monitoring in lung cancer.