Pancreatic cancer exosomes: Their role in drug resistance and immunomodulation

Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate, which is primarily attributed to its aggressive metastatic potential, poor prognosis, and the rapid development of resistance to conventional therapies. Within the PDAC microenvironment (PDAC-ME), therapeutic failure and disease progression are driven by the complex and dynamic bidirectional intercellular communications, mediated mainly by nanovesicles, particularly exosomes. In PDAC, they play a multifaceted role in advancing the disease, including acquired therapeutic resistance by promoting local invasion via inducing epithelial to mesenchymal transition (EMT), establishing pre-metastatic niches, remodelling recipient cells, stimulating angiogenesis, facilitating immune evasion, and ultimately supporting tumor cells to colonize in the distinct organs. The unique biological properties of exosomes present significant utility for clinical innovation. They also hold immense possibility as a liquid biopsy for non-invasive diagnosis and prognoris. They can also be explored as an immunologically competent nanocarrier for targeted therapeutic delivery. This comprehensive review helps to understand the cardinal features of PDAC, including metastasis, drug resistance, and immunomodulation, which are important for developing novel strategies to improve outcomes in PDAC patients significantly.