Prospects for anti-EVs therapy in the context of skin melanoma

This is the authors' abstract. We don't add key points for this paper.

Background. Extracellular vesicles (EVs) play a major role in the progression of skin melanoma: contributing to immune evasion, acquisition of resistance to drug therapy and metastasis. By affecting the assembly process of EVs as well as the secreted vesicles of tumor cells and their microenvironment, a significant reduction in the number of vesicles capable of transmitting signals and transporting macromolecules can be achieved. Thus, blocking this information transmission system at its different levels may be a new way of drug therapy of malignant neoplasms. Currently, there are a number of small synthetic molecules that disrupt the synthesis of exosomes and microvesicles (inhibitors of neutral sphingomyelinase, calpain, Rho-associated protein kinases) and their conjugates to combat exosomal mechanisms of resistance to immune checkpoint inhibitor therapy. In addition to inhibition of EVs assembly, membrane proteins of EVs (heat shock protein family HSPA / HSP70, laminin-binding integrins α3β1 and α6β) are considered as targets of targeted therapy. Some receptors providing specific fusion of vesicles with recipient cells have also been identified (CD46 receptor involved in the internalization of exosomes of a tumor cell line with brain metastases, SK-Mel-28, many adhesive molecules belonging to the family of integrins, immunoglobulins and selectins, as well as CD44 and tetraspanins. Aim. To review the available attempts to influence the biogenesis of tumor EVs (EVs) in order to develop a possible therapeutic strategy for the treatment of skin melanoma that has escaped the control of immune and targeting drugs. Materials and methods. In this work we present the results of research on melanoma of skin EVs and ways to influence EVs communication. The relevant sources were searched in web of Science, PubMed, eLibrary.ru. The Elicit tool for searching scientific articles was also used. Conclusion. In this work we analyzed the effect of small synthetic molecules, monoclonal antibodies and regulatory RNAs on different parts of tumor EVs biogenesis: assembly, secretion of EVs, and their transport. Conclusions are drawn about the validity of anti-EVs therapy to date and the possibility of its application in the aspect of skin melanoma.