Exosomes: Emerging Modulators of Pancreatic Cancer Drug Resistance

SIMPLE SUMMARY: The high mortality of pancreatic cancer (PaC) is due to different reasons: a lack of specific symptoms, an unlikely diagnosis, therapies’ paucity, and drug resistance onset. For this reason, it is of paramount importance to develop new strategies to cure this incurable malignancy. Exosomes are secreted by all kinds of cells and used for intercellular communications. They are also used by cancer cells to induce drug resistance. Understanding how PaC cells use exosomes in drug resistance onset represents a supplemental weapon to cure PaC patients. ABSTRACT: Pancreatic cancer (PaC) is one of the most lethal tumors worldwide, difficult to diagnose, and with inadequate therapeutical chances. The most used therapy is gemcitabine, alone or in combination with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the multidrug FOLFIRINOX. Unfortunately, PaC develops resistance early, thus reducing the already poor life expectancy of patients. The mechanisms responsible for drug resistance are not fully elucidated, and exosomes seem to be actively involved in this phenomenon, thanks to their ability to transfer molecules regulating this process from drug-resistant to drug-sensitive PaC cells. These extracellular vesicles are released by both normal and cancer cells and seem to be essential mediators of intercellular communications, especially in cancer, where they are secreted at very high numbers. This review illustrates the role of exosomes in PaC drug resistance. This manuscript first provides an overview of the pharmacological approaches used in PaC and, in the last part, focuses on the mechanisms exploited by the exosomes released by cancer cells to induce drug resistance.