Diagnosing pancreatic ductal adenocarcinoma using plasma extracellular vesicle RNA profiles

Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. This delay is caused by lack of non-invasive screening, or tests for early diagnosis, in addition to rapid disease progression with non-specific symptoms. Most patients present with unresectable disease, and outcomes are consequently poor. Furthermore, advances in surgical techniques, perioperative management and oncological treatments have made limited impact on overall survival. This is true even despite our improved understanding of PDAC genetic/transcriptional landscapes, molecular subtypes, intra-/inter-tumoural heterogeneity and innovative therapeutics. As early diagnosis is vital for prolonging survival, there is an urgent need for reliable, highly sensitive and specific biomarkers. Blood-based biomarkers are an ideal choice due to their relatively low cost, minimal invasiveness and accessibility for repeated sampling. However, these biomarkers should also be able to stage the disease, as well as provide prognostic/predictive information to guide clinical decisions, especially since selection and timing of therapeutic modalities can be critical.1 Extracellular vesicles (EVs; exosomes, microvesicles and apoptotic bodies) are lipid bilayer structures found in biofluids that contain cell-derived bioactive molecules, including nucleic acids.2 EVs have recently emerged as critical mediators of communication between tumour cells and also the surrounding microenvironment.3 EVs can transmit information to recipient cells by acting at cell surface, releasing their cargo through membrane fusion, or may be internalised via endocytosis.4 Importantly, transferred EV components are functional and influence the phenotype of recipient cells,5 6 including …