IMMUNOMODULATORY AND ANTITUMOR POTENTIAL OF RNA INTERFERENCE

Abstract

The aim of the work: to summarize the existing results in antitumor RNAi therapy, as well as to highlight the role of siRNA as a remodulator of the immune response in oncological diseases.

Materials and methods: the literature review includes an analysis of scientific papers from the PubMed, Embase, eLIBRARY, CyberLeninka and Web of Science, CNKI and MEDLINE databases

Results: The importance of cancer problem is due to the immune tolerance of tumors, their drug resistance, and a number of limitations in the use of traditional treatment methods. RNA interference (RNAi)-based approaches, which can be implemented using small interfering RNA (siRNA) molecules, can offer promising therapeutic tactics that will combine a immunomodulatory effect and targeted suppression of gene expression important for tumor growth. Inhibition of tumor regulatory pathways will disrupt 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. A study of this approach on an in vivo model in laboratory conditions led to a decrease in the volume of melanoma, breast tumors and hepatocellular carcinoma up to 5 times, suppression of metastasis and an increase in overall survival.

Conclusions: Cancer - 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, the use of checkpoint inhibitors and targeted antitumor agents, the effectiveness of current approaches islimited by the immunosuppressive environment of the tumor, heterogeneity of malignant cells, side effects and toxicity of the drugs themselves. RNAi is a promising approach that can simultaneously solve several key problems of oncoimmunology, such as suppression of the expression of critical 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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