Optimizing Gene Silencing Strategies for Pancreatic Cancer

Pancreatic cancer is a devastating malignancy with a median survival of less than one year. The exceedingly poor prognosis for metastatic pancreatic cancer patients remains a significant unmet medical need and is an opportunity for development of novel therapeutic approaches incorporating gene therapy strategies. Barriers exist preventing effective gene therapy including low transfection efficiency, poor tissue penetrance as well as non-specific delivery. However, one specific strategy using synthetic short interfering RNA fragments holds great potential and recently demonstrated successful systemic delivery using a transferrin (Tf)-targeted cyclodextrin-based polymer nanoparticle. Various nanoparticle formulations are currently being optimized for systemic gene therapy approaches. In this review, we highlight the rapidly progressing field of gene therapy strategies that have the potential to enhance the care of patients with devastating malignancies such as pancreatic cancer and focus on systemic delivery strategies to overcome remaining hurdles limiting widespread clinical applications.