Prospects of epigenetic therapy of head and neck squamous cell carcinoma

Abstract

Introduction. Head and neck squamous cell carcinoma is the 6th most common malignant tumor. It is characterized by immune response evasion and drug resistance. To stimulate antitumor immune response, antibodies against such cell cycle checkpoints as programmed cell death 1 (pD-1) and programmed death-ligand 1 (pD-L1) are used. However, effectiveness of monotherapy with these checkpoint inhibitors turned out to be low, and combinations with other antitumor drugs have high risk of adverse events.Aim. To determine the most practical ways to influence epigenetic factors in treatment of head and neck squamous cell carcinoma.Materials and methods. Scientific literature published between 2011 and 2022 and indexed in the eLIBRARY, Scopus, woS, NCBI databases (398 articles, of which 76 were used) was analyzed.Results. prospects of development of epigenetic stimulation of expression of retroelements located in tumor genomes through inhibition of DNA methyltransferases, deacetylases and histone methyltransferases were considered. when retroelements are activated, their transcripts form double-stranded RNA stimulating T killers and interferon response (virus mimicry). for DNA methyltransferase inhibitors, restoration of tumor suppressor genes which are hypermethylated in squamous cell carcinoma is also observed. However, retroelement activation is a driver mechanism of carcinogenesis, and their nonspecific expression can lead to tumor progression and formation of secondary tumors. Therefore, in the virus mimicry method it is practical to use as targets microRNA complementary to retroelements which recruit epigenetic factors to their loci (RNA-directed DNA methylation), as well as antisense oligonucleotides against oncogenic microRNA associated with retroelements. These approaches allow to inhibit retroelements participating in carcinogenesis. Nonspecific method of retrotransposon activity suppression is being developed in antitumor therapy, but data show successful application of only reverse transcriptase inhibitors preventing insertions and progression of genomic instability. we have performed analysis of scientific literature on transposable elements-derived microRNA associated with head  and  neck  squamous  cell  carcinoma.  As  a  result,  31  microRNAs  were  identified,  derived  from:  LINE:  miR-1249, -151a, -211, -2355, -28, -31, -3144, -374a, -374b, -421, -450b, -511, -576, -577, -582, -708, -769, -887, -95; HERv: miR-1269a,  -1911,  -3200,  -495;  non-autonomous  SINE:  miR-335,  -342,  -378a,  -3934,  -487b;  DNA  transposons:  miR-224, -584, -652. These microRNAs can serve as the basis for epigenetic therapy of head and neck squamous cell carcinoma.