Evolution of Liquid Biopsies for Detecting Pancreatic Cancer

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterised by late diagnosis and poor prognosis, with current diagnostic and prognostic strategies proving insufficient. Liquid biopsy techniques, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and proteomics, present potential avenues for enhancing PDAC diagnosis, prognosis, and management. A review of literature from 2019 to 2024 identified 49 relevant studies focusing on these biomarkers. Investigations into ctDNA, particularly in detecting mutant KRAS, have shown some diagnostic and prognostic potential, though its efficacy in early-stage disease remains limited. CTCs, whilst highly specific, exhibit similarly restricted diagnostic utility in early disease, and studies have yielded inconsistent prognostic findings. Exosomal research identifies diverse biomarkers with promising diagnostic and prognostic value. Importantly, proteomics demonstrates superior accuracy in PDAC diagnosis, including early-stage detection, and significant prognostic capacity, especially when combined with CA19-9 analysis. This review highlights the significance of continued research into liquid biopsy techniques to improve PDAC management and outcomes.Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterised by late diagnosis and poor prognosis. Despite advancements, current diagnostic and prognostic strategies remain limited. Liquid biopsy techniques, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), circulating tumour exosomes, and proteomics, offer potential solutions to improve PDAC diagnosis, prognostication, and management. A systematic search of Ovid MEDLINE identified studies published between 2019 and 2024, focusing on liquid biopsy biomarkers for PDAC. A total of 49 articles were included. ctDNA research shows some promise in diagnosing and prognosticating PDAC, especially through detecting mutant KRAS in minimal residual disease assays. CTC analyses had low sensitivity for early-stage PDAC and inconsistent prognostic results across subpopulations. Exosomal studies revealed diverse biomarkers with some diagnostic and prognostic potential. Proteomics, although relatively novel, has demonstrated superior accuracy in PDAC diagnosis, including early detection, and notable prognostic capacity. Proteomics combined with CA19-9 analysis has shown the most promising results to date. An update on multi-cancer early detection testing, given its significance for population screening, is also briefly discussed. Liquid biopsy techniques offer promising avenues for improving PDAC diagnosis, prognostication, and management. In particular, proteomics shows considerable potential, yet further research is needed to validate existing findings and comprehensively explore the proteome using an unbiased approach.