Toward a Better Understanding of Pancreatic Ductal Adenocarcinoma Glimmers of Hope?

Pancreatic ductal adenocarcinoma (PDAC) imposes a heavy burden of disease, especially in the most developed countries, and the mortality rate has not declined over the past decades. Therefore, there is an urgent need for a better understanding of the molecular mechanisms of PDAC, which may help to improve early detection, prognosis, and treatment efficiency. This review focuses on PDAC epidemiology and on recent advances in our understanding of the molecular mechanisms of PDAC carcinogenesis. We discuss the cancer stem cell hypothesis, which provides a rationale for the pervasive resistance of PDAC to chemoradiotherapy and explains the disease recurrence after the currently used genotoxic treatment. Identification of an inherited predisposition to PDAC due to genetic factors should allow high-risk groups to benefit from early detection programs. The presence in biofluids of stable tumor-specific microRNAs (miRs) makes them the most promising biomarkers potentially capable of detecting tumors long before their clinical manifestation. The cancer stem cell hypothesis made it realistic to anticipate a clinical impact of miR-based therapy (miR mimics and antagomirs) to overcome the otherwise insurmountable barrier of frequent resistance of PDAC to chemoradiotherapy. The investigation of miRs in PDAC may provide exciting novel strategies for both diagnosis and treatment.