Clinical applications of selected liquid biopsy biomarkers in pancreatic cancer with a focus on ctDNA CTCs and exosome derived biomarkers

Pancreatic ductal adenocarcinoma (PDAC) remains a major clinical challenge because reliable biomarkers for early detection, risk stratification, and treatment monitoring are still limited. Liquid biopsy has emerged as a promising complementary approach that enables minimally invasive assessment of tumor-derived material in body fluids. This review focuses on three selected and widely investigated liquid-biopsy biomarker classes in PDAC—ctDNA, CTCs, and exosome-derived biomarkers—because they map onto complementary molecular, cellular, and extracellular-vesicle compartments and have been evaluated across clinically relevant settings including diagnosis, prognosis, treatment monitoring, and minimal residual disease (MRD) assessment. We summarize their biological basis, detection strategies, and clinical applications in early detection, prognostic assessment, treatment monitoring, and minimal residual disease (MRD) evaluation. We also discuss assay selection in KRAS -wild-type disease, factors influencing ctDNA shedding, postoperative sampling timing, and the contribution of anatomically enriched body fluids such as bile and pancreatic juice. Current evidence indicates that ctDNA is the most mature platform for molecular profiling, prognostic assessment, treatment monitoring, and MRD research, although sensitivity remains limited in localized disease. CTCs provide intact cellular information and may offer prognostic value, but their rarity in peripheral blood and methodological heterogeneity limit routine use. Exosome-derived biomarkers are abundant and relatively stable, making them attractive for multiparametric diagnostic and prognostic models, although tumor specificity, isolation methods, and assay standardization remain substantial challenges. Overall, no single liquid-biopsy platform is sufficient for all PDAC scenarios. Future progress will require standardized methods, prospective clinical validation, and integrated biomarker strategies combined with established clinical parameters.