Gene silencing delivery systems for the treatment of pancreatic cancer: Where and what to target next?

Despite intensive research efforts and development of numerous new anticancer drugs and treatment strategies over the past decades, there has been only very limited improvement in overall patient survival and in effective treatment options for pancreatic cancer. Current chemotherapy improves survival in terms of months and death rates in pancreatic cancer patients are almost equivalent to incidence rates. It is imperative to develop new therapeutic approaches. Among them, gene silencing shows promise of effectiveness in both tumor cells and stromal cells by inhibiting tumor-promoting genes. This review summarizes potential targets for gene silencing in both pancreatic cancer cells and abundant stromal cells focusing on non-viral delivery systems for small RNAs and discusses the potential immunological implications. The review concludes with the importance of multifactorial therapy of pancreatic cancer.