Managing Pancreatic Adenocarcinoma: A Special Focus in MicroRNA Gene Therapy

Pancreatic cancer is an aggressive disease and the fourth most lethal cancer in developed countries. Despite all progress in medicine and in understanding the molecular mechanisms of carcinogenesis, pancreatic cancer still has a poor prognosis, the median survival after diagnosis being around 3 to 6 months and the survival rate of 5 years being less than 4%. For pancreatic ductal adenocarcinoma (PDAC), which represents more than 90% of new pancreatic cancer cases, the prognosis is worse than for the other cancers with a patient mortality of approximately 99%. Therefore, there is a pressing need for developing new and efficient therapeutic strategies for pancreatic cancer. In this regard, microRNAs not only have been seen as potential diagnostic and prognostic molecular markers but also as promising therapeutic agents. In this context, this review provides an examination of the most frequently deregulated microRNAs (miRNAs) in PDAC and their putative molecular targets involved in the signaling pathways of pancreatic
carcinogenesis. Additionally, it is presented a summary of gene therapy clinical trials involving miRNAs and it is illustrated the therapeutic potential associated to these small non-coding RNAs, for PDAC treatment. The facts presented here constitute a strong evidence of the remarkable opportunity associated to the application of microRNA-based therapeutic strategies as a novel approach for cancer therapy.