Advances in Liquid Biopsy for Precision Oncology: Applications, Challenges, and Future Directions in Clinical Laboratories

Abstract

: Liquid biopsy has emerged as a revolutionary, minimally invasive approach in precision oncology, enabling dynamic molecular profiling of tumors through analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and other biomarkers in body fluids. Focusing specifically on recent advances from 2023 to 2026, this review provides a laboratory-centered critical synthesis addressing the core operational questions for clinical implementation: which liquid biopsy platform should be selected for specific analytes and clinical intents, under what pre-analytical and analytical constraints, and with what quality-control and clinical utility standards. Key technological developments include highly sensitive next-generation sequencing (NGS) with unique molecular identifiers (UMIs), digital droplet PCR (ddPCR), multi-omics integration, and artificial intelligence-assisted interpretation, which have improved detection sensitivity to ultra-low variant allele frequencies. Major clinical applications encompass multi-cancer early detection (MCED), companion diagnostics, real-time treatment monitoring, minimal residual disease (MRD) assessment, and resistance mutation tracking. These tools often provide earlier insights than imaging and better capture tumor heterogeneity. Compared with tissue biopsy, liquid biopsy offers advantages in repeatability, speed, and systemic representation, though challenges remain in sensitivity for early-stage disease, standardization, cost-effectiveness, and implementation in grassroots hospitals. Future directions emphasize multi-omics, AI, and automated workflows to enhance its role across the cancer continuum. This review highlights practical recommendations for clinical laboratories