Liquid biopsy in pancreatic cancer: current advances, limitations, and future perspectives

: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is usually diagnosed at advanced stages. The diagnosis of PDAC is established through pancreatic cytology/tissue biopsy, most commonly obtained under endoscopic ultrasound-guidance. Although this approach is generally safe and accurate for the histological diagnosis, maintaining/obtaining material for additional molecular analysis may be challenging. Thus, there is growing interest in minimally invasive approaches capable of providing molecular information without necessarily requiring tissue sampling. Liquid biopsy (LB) represents a significant advancement in this regard, being a minimally invasive tool for biomarker analysis and with the potential to improve patient management at various levels. The most relevant biomarkers that LB can detect are circulating tumor cells, cell-free DNA, circulating miRNA, and extracellular vesicles. Integrating LB into the clinical workflow may improve the diagnosis, prognosis, and monitoring of the disease, even for patients affected by PDAC and with potential implications on early detection approaches. Despite significant progress, no LB assay is yet validated for routine PDAC management; however, growing evidence suggests that multimodal LB integration may soon reshape diagnostic and surveillance strategies. Here we provide a comprehensive overview on liquid biopsy in pancreatic cancer, presenting its current progress, limitations, and future perspectives.