Review of molecular mechanisms underlying gemcitabine resistance in pancreatic cancer

Pancreatic cancer is one the most malignant cancers in human. A great percentage of patients die annually due to lack of early detection as well as efficient treatment strategies. Only five-year survival rate is still only seen in 5% of patients. Major problem of this deadly disease is the intrinsic and acquired resistance to current chemotherapeutic agents such as gemcitabine. So far, different molecular mechanisms are attributed to gemcitabine resistance. For instance, genetic mechanisms, aberrant gene expression in cellular signaling pathways, cancer stem cells, impaired apoptosis related genes, epigenetic changes and potential role of microRNAs have been identified in gemcitabine resistance of pancreatic cancer. Improving the drug efficacy and overcoming to drug resistance is the current goal in treatment of pancreatic cancer. Understanding the cellular and molecular mechanisms of resistance can help us to develop novel therapeutic approaches leading to increased effectiveness of current treatments. In this review, we summarized the molecular mechanisms involved in gemcitabine resistance in pancreatic cancer.