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

Abstract

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 oligonucleotides (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.

Downregulation of thymidylate synthase by RNAi molecules enhances the antitumor effect of pemetrexed in an orthotopic malignant mesothelioma xenograft mouse model

“…These results emphasize the pivotal relevance of RNAi as an effective tool for increasing the therapeutic efficacy of PMX against human MPM. RNA interference (RNAi), a sequence-specific gene silencing mechanism induced by double-stranded RNA (dsRNA), has emerged as a promising therapy for combating cancer (19,33,34). The RNAi effect can be mediated with short interfering RNA (siRNA), which is a short, double stranded RNA with 21-23 base pairs (35), or, as recently demonstrated, with short hairpin RNA (shRNA) (36).…”

Combined therapy with a thymidylate synthase-inhibiting vector and S-1 has effective antitumor activity against 5-FU-resistant tumors

“…Regarding the method for the downregulation of the target genes, RNAi has recently become a powerful technique for such gene therapy (13). RNAi is a conserved biological process by which dsRNA inhibits gene expression in a sequencedependent manner.…”

“…Recently, RNA interference (RNAi), a sequence-specific gene silencing process initiated with double-stranded RNA (dsRNA), has been developed to be a powerful tool to inhibit expressions of specific genes (12,13). Considering the fact that a high level of the intratumoral TS expression is associated with 5-FU-resistance and a poor outcome in cancer patients treated with 5-FU-derived agents (8)(9)(10), the suppression of TS expression by RNAi might restore the responsiveness to 5-FU in 5-FU-resistant tumors.…”

Nano based drug delivery

“…are examined in infrared spectroscopy for the characterization of dendrimers. Disappearance of nitrile groups or amine groups and the appearance or disappearance of hydrogen bonds indicates the synthesis and surface modification of dendrimers [145,146].…”