Potential to use of viral reverse transcriptase inhibitors in oncology

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 Sco...

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Main Authors: O. A. Vlasova, I. A. Antonova, Kh. M. Magomedova, M. A. Usolkina, K. I. Kirsanov, G. A. Belitsky, T. T. Valiev, M. G. Yakubovskaya
Format: Article
Language:Russian
Published: ABV-press 2024-06-01
Series:Успехи молекулярной онкологии
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Online Access:https://umo.abvpress.ru/jour/article/view/673
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author O. A. Vlasova
I. A. Antonova
Kh. M. Magomedova
M. A. Usolkina
K. I. Kirsanov
G. A. Belitsky
T. T. Valiev
M. G. Yakubovskaya
author_facet O. A. Vlasova
I. A. Antonova
Kh. M. Magomedova
M. A. Usolkina
K. I. Kirsanov
G. A. Belitsky
T. T. Valiev
M. G. Yakubovskaya
author_sort O. A. Vlasova
collection DOAJ
description 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.
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series Успехи молекулярной онкологии
spelling doaj-art-50ce600013924932ab99b89de763f8242025-08-20T03:00:54ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872024-06-0111282810.17650/2313-805X-2024-11-2-8-28324Potential to use of viral reverse transcriptase inhibitors in oncologyO. A. Vlasova0I. A. Antonova1Kh. M. Magomedova2M. A. Usolkina3K. I. Kirsanov4G. A. Belitsky5T. T. Valiev6M. G. Yakubovskaya7N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological UniversityM.V. Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological UniversityN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Peoples’ Friendship University of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Sechenov University, Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaIn 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.https://umo.abvpress.ru/jour/article/view/673reverse transcriptase inhibitorsreverse transcriptaseline1 long dispersed repeatstelomerase activity inhibitors
spellingShingle O. A. Vlasova
I. A. Antonova
Kh. M. Magomedova
M. A. Usolkina
K. I. Kirsanov
G. A. Belitsky
T. T. Valiev
M. G. Yakubovskaya
Potential to use of viral reverse transcriptase inhibitors in oncology
Успехи молекулярной онкологии
reverse transcriptase inhibitors
reverse transcriptase
line1 long dispersed repeats
telomerase activity inhibitors
title Potential to use of viral reverse transcriptase inhibitors in oncology
title_full Potential to use of viral reverse transcriptase inhibitors in oncology
title_fullStr Potential to use of viral reverse transcriptase inhibitors in oncology
title_full_unstemmed Potential to use of viral reverse transcriptase inhibitors in oncology
title_short Potential to use of viral reverse transcriptase inhibitors in oncology
title_sort potential to use of viral reverse transcriptase inhibitors in oncology
topic reverse transcriptase inhibitors
reverse transcriptase
line1 long dispersed repeats
telomerase activity inhibitors
url https://umo.abvpress.ru/jour/article/view/673
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AT iaantonova potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT khmmagomedova potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT mausolkina potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT kikirsanov potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT gabelitsky potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT ttvaliev potentialtouseofviralreversetranscriptaseinhibitorsinoncology
AT mgyakubovskaya potentialtouseofviralreversetranscriptaseinhibitorsinoncology