Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press67310.17650/2313-805X-2024-11-2-8-28REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИPotential to use of viral reverse transcriptase inhibitors in oncologyПотенциальные возможности использования в онкологии ингибиторов обратной транскриптазы вирусовhttps://orcid.org/0000-0002-1498-849XVlasovaO. A.ВласоваО. А.
Russian Federation

Olga Aleksandrovna Vlasova

115522; 24 Kashirskoe Shosse; Moscow

Ольга Александровна Власова

115522; Каширское шоссе, 24; Москва

olya_vlasov@mail.ruhttps://orcid.org/0009-0004-3482-8954AntonovaI. A.АнтоноваИ. А.
Russian Federation

115522; 24 Kashirskoe Shosse; Moscow

115522; Каширское шоссе, 24; Москва

https://orcid.org/0009-0004-8514-3859MagomedovaKh. M.МагомедоваХ. М.
Russian Federation

115522; 24 Kashirskoe Shosse; 119671; 86 Vernadsky Prospekt; Moscow

115522; Каширское шоссе, 24; 119671; пр-кт Вернадского, 86; Москва

UsolkinaM. A.УсолкинаМ. А.
Russian Federation

119671; 86 Vernadsky Prospekt; Moscow

119671; пр-кт Вернадского, 86; Москва

https://orcid.org/0000-0002-8599-6833KirsanovK. I.КирсановК. И.
Russian Federation

115522; 24 Kashirskoe Shosse; 117198; 6 Miklukho-Maklaya St.; Moscow

115522; Каширское шоссе, 24; 117198; ул. Миклухо-Маклая, 6; Москва 

https://orcid.org/0000-0002-3167-7204BelitskyG. A.БелицкийГ. А.
Russian Federation

115522; 24 Kashirskoe Shosse; Moscow

115522; Каширское шоссе, 24; Москва

https://orcid.org/0000-0002-1469-2365ValievT. T.ВалиевТ. Т.
Russian Federation

115522; 24 Kashirskoe Shosse; 119048; Bld. 2, 8 Trubetskaya St.; Moscow

115522; Каширское шоссе, 24; 119048; ул. Трубецкая, 8, стр. 2;  Москва 

https://orcid.org/0000-0002-9710-8178YakubovskayaM. G.ЯкубовскаяМ. Г.
Russian Federation

115522; 24 Kashirskoe Shosse; Moscow

115522; Каширское шоссе, 24; Москва

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииM.V. Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological UniversityИнститут тонких химических технологий им. М.В. Ломоносова ФГБОУ ВО «МИРЭА – Российский технологический университет»Peoples’ Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»Sechenov University, Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России150520241128282706202427062024Copyright ©; 2024, Vlasova O.A., Antonova I.A., Magomedova K.M., Usolkina M.A., Kirsanov K.I., Belitsky G.A., Valiev T.T., Yakubovskaya M.G.Copyright ©; 2024, Власова О.А., Антонова И.А., Магомедова Х.М., Усолкина М.А., Кирсанов К.И., Белицкий Г.А., Валиев Т.Т., Якубовская М.Г.2024Vlasova O.A., Antonova I.A., Magomedova K.M., Usolkina M.A., Kirsanov K.I., Belitsky G.A., Valiev T.T., Yakubovskaya M.G.Власова О.А., Антонова И.А., Магомедова Х.М., Усолкина М.А., Кирсанов К.И., Белицкий Г.А., Валиев Т.Т., Якубовская М.Г.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/673

   In preparing the review, articles on the functioning of the reverse transcriptase enzyme of endogenous repeat sequences LINE1, the mechanisms of action and antitumor activity of viral reverse transcriptase inhibitors. Articles available in the biomedical literature information databases SciVerse Scopus, PubMed, Web of Science, Russian Science CitationIndex (RSCI) were analyzed. The review used information from 140 publications, of which 95 and 39 were published, respectively, over the last ten and three years, 2 articles present the results of clinical studies, and 45 articles refer to results demonstrating the anticancer properties of the studied compounds in various models in vitro and in vivo.

   Aim. Based on data on the functional properties of the reverse transcriptase enzyme of endogenous repeat sequences LINE1 (long interspersed nuclear elements 1), analyze the potential use of viral reverse transcriptase inhibitors in oncology, presenting their classification and main mechanisms of action.

   About 98 % of the human genome consists of repetitive sequences, most of which are represented by mobil genetic elements, the activation of which leads to increased genome instability. These include long (LINE) and short (SINE) interspersed nuclear element repeated DNA sequences interspersed nuclear elements, respectively, which occupy about 45 % of the human genome. Increased expression levels of these sequences in the genome have been identified in many forms of malignant neoplasms. Their transposition occurs due to the expression of LINE1-encoded reverse transcriptase, whichis homologous to viral reverse transcriptase. To date, reverse transcriptase inhibitors of viruses of nucleoside and non-nucleoside structure have been developed and are successfully used in the clinic. These drugs demonstrate an inhibitory effect on both LINE1 reverse transcriptase and telomerase, which provides the tumor cell with the ability to overcome replicative senescence. Due to these properties, these compounds are expected to exhibit both their own antitumor activity and increase the sensitivity of tumor cells to the therapy of malignant neoplasms, which is experimentally confirmed in models of malignant tumors in vitro and in vivo. Use of reverse transcriptase inhibitors in combination therapy seems advisable both to prevent further genome rearrangements caused by LINE1 and to suppress the survival of tumor cells by inhibiting telomerase activity.

   В работе проанализированы статьи, посвященные изучению функционирования фермента обратной транскриптазы эндогенных повторяющихся последовательностей LINE1, механизмов действия и противоопухолевой активности ингибиторов обратной транскриптазы вирусов, имеющиеся в информационных базах биомедицинской литературы SciVerse Scopus, PubMed, Web of Science и РиНЦ (Российский индекс научного цитирования). В обзоре использована информация 140 работ, 95 и 39 из которых были опубликованы в течение 10 и 3 последних лет соответственно; 2 работы представляют собой результаты клинических исследований, а в 45 описаны противоопухолевые свойства исследуемых соединений на различных моделях in vitro и in vivo.

   Цель работы – на основании данных о функциональных свойствах фермента обратной транскриптазы эндогенных повторяющихся последовательностей LINE1 (long interspersed nuclear elements 1) проанализировать потенциальную возможность использования в онкологии ингибиторов обратной транскриптазы вирусов, представив их классификацию и основные механизмы действия.

   Около 98 % генома человека составляют повторяющиеся последовательности, в основном мобильные генетические элементы, активация которых приводит к повышению нестабильности генома. В их число входят длинные (LINE) и короткие (short interspersed nuclear element, SINE) повторяющиеся последовательности ДНК, занимающие около 45 % генома человека. Повышения уровня экспрессии этих последовательностей в геноме выявлены при многих формах злокачественных новообразований. их транспозиция происходит благодаря экспрессии кодируемой LINE1 обратной транскриптазы, гомологичной обратной транскриптазе вирусов. к настоящему времени разработаны и успешно применяются в клинической практике ингибиторы обратной транскриптазы вирусов нуклеозидной и ненуклеозидной структур. Эти препараты демонстрируют ингибирующее действие как на обратную транскриптазу LINE1, так и на теломеразу, которая обеспечивает способность опухолевой клетки преодолевать репликативное старение. Благодаря этим свойствам, данные соединения, как ожидается, должны проявлять собственную противоопухолевую активность и повышать чувствительность опухолевых клеток к проводимой терапии злокачественных новообразований, что экспериментально подтверждается на моделях злокачественных новообразований in vitro и in vivo. Таким образом, использование в комбинированной терапии ингибиторов обратной транскриптазы представляется целесообразным как для предотвращения дальнейших перестроек генома, вызываемых LINE1, так и для подавления выживаемости опухолевых клеток путем ингибирования теломеразной активности.

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