The Role of Exosomes in Pancreatic Ductal Adenocarcinoma Progression and Their Potential as Biomarkers

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a dismal five-year survival rate. Despite remarkable improvements of cancer therapeutics in recent years, patients with PDAC barely benefit from them due to late diagnosis of the disease. Exosomes, small extracellular vesicles with a diameter of approximately 30 to 150 nm, play a significant role in cell–cell communication via cargo delivery (e.g., proteins, lipids, and nucleic acids) among heterogeneous populations. Emerging studies have suggested that exosomes with specific surface markers or contents are capable of discriminating PDAC patients from health individuals. Because detectable in several body fluids, such as blood, urine and saliva, exosomes are considered as promising liquid biopsies for early detection and disease monitoring. In this review, we shed light on the involvement of exosomes and their cargos in PDAC progression and their feasibility as diagnostic and prognostic biomarkers. In addition, limitations and urgent problems required further investigation are also discussed in our review. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, is an aggressive and lethal cancer with a dismal five-year survival rate. Despite remarkable improvements in cancer therapeutics, the clinical outcome of PDAC patients remains poor due to late diagnosis of the disease. This highlights the importance of early detection, wherein biomarker evaluation including exosomes would be helpful. Exosomes, small extracellular vesicles (sEVs), are cell-secreted entities with diameters ranging from 50 to 150 nm that deliver cellular contents (e.g., proteins, lipids, and nucleic acids) from parent cells to regulate the cellular processes of targeted cells. Recently, an increasing number of studies have reported that exosomes serve as messengers to facilitate stromal-immune crosstalk within the PDAC tumor microenvironment (TME), and their contents are indicative of disease progression. Moreover, evidence suggests that exosomes with specific surface markers are capable of distinguishing patients with PDAC from healthy individuals. Detectable exosomes in bodily fluids (e.g., blood, urine, saliva, and pancreatic juice) are omnipresent and may serve as promising biomarkers for improving early detection and evaluating patient prognosis. In this review, we shed light on the involvement of exosomes and their cargos in processes related to disease progression, including chemoresistance, angiogenesis, invasion, metastasis, and immunomodulation, and their potential as prognostic markers. Furthermore, we highlight feasible clinical applications and the limitations of exosomes in liquid biopsies as tools for early diagnosis as well as disease monitoring. Taking advantage of exosomes to improve diagnostic capacity may provide hope for PDAC patients, although further investigation is urgently needed.