Pancreatic cancer stem cells and therapeutic approaches

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (∼6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis. PDAC is characterized by molecular alterations, including mutations of K-RAS (∼90% of cases), TP53, transforming growth factor-β, Hedgehog, WNT and NOTCH signaling pathways. Given that cancer stem cells have a crucial role not only in tumor initiation and progression, but also in drug resistance and relapse or recurrence of various cancer types, they may be excellent targets for effective novel therapeutic approaches. Here, we reviewed recent therapeutic strategies targeting pancreatic cancer stem cells using chemotherapeutics and targeted drugs, non-coding RNAs (i.e., siRNA and miRNAs), immunotherapy, and natural compounds.