Small interfering RNA therapy in cancer: mechanism, potential targets, and clinical applications

Background: Small interfering RNA (siRNA) has become a powerful tool in knocking down or silencing gene expression in most cells. siRNA-based therapy has shown great promise for many diseases such as cancer. Major targets for siRNA therapy include oncogenes and genes that are involved in angiogenesis, metastasis, survival, antiapoptosis and resistance to chemotherapy. Objectives: This review briefly summarizes current advances in siRNA therapy and clinical applications in cancers, especially in pancreatic cancer. Methods: This review article covers several aspects of siRNA therapy in cancer, which include the types of siRNA, the delivery systems for siRNA, and the major targets for siRNA therapy. Specific attention is given to siRNA in pancreatic cancer, which is our main research focus. Results/conclusion: siRNA can be introduced into the cells by using either chemically synthesized siRNA oligonucleoticles (oligos), or vector-based siRNA (shRNA), which allows long lasting and more stable gene silencing. Nanoparticles and liposomes are commonly used carriers, delivering the siRNA with better transfection efficiency and protecting it from degradation. In combination with standard chemotherapy, siRNA therapy can also reduce the chemoresistance of certain cancers, demonstrating the potential of siRNA therapy for treating many malignant diseases. This review will provide valuable information for clinicians and researchers who want to recognize the newest endeavors within this field and identify possible lines of investigation in cancer.