Liquid Biopsy and Circulome-Based Biomarkers in Pancreatic Ductal Adenocarcinoma: Advances, Challenges, and Clinical Translation

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal malignancies, largely due to late-stage diagnosis and the limitations of conventional tissue biopsy. Liquid biopsy, the analysis of tumor-derived components in biofluids, has emerged as a promising minimally invasive tool for early detection, molecular profiling, and monitoring of PDA. This review comprehensively examines the current landscape of liquid biopsy biomarkers in PDA, including circulating tumor DNA (ctDNA), RNA (ctRNA), extracellular vesicles (EVs), proteins, and metabolites. We highlight the diagnostic and prognostic potential of individual and combined biomarkers, with a focus on the emerging circulome approach, the integrative analysis of multiple analyte classes to enhance sensitivity and specificity. While significant progress has been made, clinical application faces challenges such as biomarker heterogeneity, low analyte abundance, and technical variability in detection platforms. Advances in bioinformatics, deep sequencing, and unique molecular identifier (UMI) strategies are crucial to overcoming these obstacles. This review synthesizes recent evidence, presents comparative tables of key biomarkers and methodologies, and discusses future directions for the validation and implementation of liquid biopsy in the precision oncology of PDA.

کلیدواژه ها:

Pancreatic Ductal Adenocarcinoma ، Liquid Biopsy ، Circulating Tumor DNA ، Circulome ، Biomarkers ، Precision Oncology