Gemcitabine, a nucleoside analog drug, is the current standard of care for the treatment of pancreatic cancer. Its effects are suboptimal partly due to cellular mechanisms limiting its transport, activation, and overall efficacy. Nonetheless, novel therapeutic approaches are presently under study to circumvent gemcitabine resistance in pancreatic cancer. Specifically, microRNA (miRNA) control of gemcitabine chemoresistance will be discussed. With these new approaches come additional challenges to be addressed. The presentation summarizes the determinants of chemoresistance in the gemcitabine cytotoxicity pathways, provides an overview of miRNA investigational approaches for
overcoming chemoresistance, and discusses new challenges presented. Understanding the future directions of the field may assist in the successful development of novel treatment strategies for enhancing chemotherapeutic efficacy in pancreatic cancer.