Antitumor effects of small interfering RNAs

The aim of our work was to summarize the existing results in anticancer therapy with small interfering RNAs (siRNAs), as well as to highlight the role of siRNA as a remodulator of the immune response in oncological diseases. The literature review includes an analysis of research publications from the PubMed, Embase, eLIBRARY, CyberLeninka and Web of Science, CNKI and MEDLINE databases. Sufficient challenges in cancer treatment occur due to the immune tolerance of tumors, their drug resistance, and a number of limitations in usage of conventional treatment schedules. The novel RNA interference (RNAi)-based approaches, may be implemented using small interfering RNA (siRNA) molecules. These methods may offer promising therapeutic strategies that will promote an immunomodulatory effect and targeted suppression of gene expression important for tumor growth. Inhibition of tumor regulatory pathways will affect tumor proliferation and metastasis, while mobilizing antitumor immunity through stimulation of Toll-like receptors, maturation of dendritic cells, and infiltration of cytotoxic T lymphocytes into the tumor. The in vivo studies of this approach in experimental models showed a decrease in the volume of melanoma, breast tumors and hepatocellular carcinoma up to 5 times, suppression of metastasis and increased overall survival. Cancer treatment is among the most significant problems of modern medicine, characterized by high mortality, mechanisms of immune tolerance and frequent emergence of resistance to existing therapeutic approaches. Despite the progress in modern oncoimmunology, usage of checkpoint inhibitors and targeted antitumor agents, the effectiveness of current approaches is limited by immunosuppressive microenvironment of tumors, heterogeneity of malignant cells, adverse effects and toxicity of the drug therapy. RNAi treatment is a promising approach that can simultaneously solve several key problems of oncoimmunology, such as suppression of the driver oncogenes; blocking tumor signaling pathways; as well as activation of innate immunity. The dual effect of RNAi, which consists of a direct effect on tumor cells and immune modulation of the tumor environment, makes RNAi an excellent tool for overcoming tumor immunotolerance and providing a direct cytotoxic antitumor effect. 

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