Pathophysiology roles and translational opportunities of miRNAs in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest human cancers, with 6months of median survival. PDAC is the fourth-leading cause of cancer mortality. Intrinsic resistance to chemotherapeutics and a lack of effective therapies are the major factors contributing to this poor prognosis. Due to nonspecific symptoms and the unavailability of early diagnostic tools, the majority of patients are diagnosed at an advanced stage, for which the 5-year survival rate is 3%. PDAC is associated with genetic alterations, including KRAS mutations (detected in ~90% of cases) and inactivation of tumor suppressors, such as TP53 (~70%), SMAD4 (20%-50%), and CDKN2A (50%-90%), as well as a unique tumor microenvironment with excessive stroma, promoting tumor growth and contributing to treatment failures.