Approaches to anticancer therapy based on modulation of DNA methylation

Background. DNA methylation is a crucial mechanism of epigenetic regulation of transcription. Disturbances in DNA methylation mechanism are associated with various malignancies such as acute myeloid leukaemia, breast cancer, prostate cancer, etc. Influencing the functional status of DNA methyltransf...

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Main Authors: V. P. Maksimova, J. V. Makus, V. G. Popova, O. G. Usalka, G. A. Belitsky, M. G. Yakubovskaya, K. I. Kirsanov
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2024-09-01
Series:Сибирский онкологический журнал
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Online Access:https://www.siboncoj.ru/jour/article/view/3199
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author V. P. Maksimova
J. V. Makus
V. G. Popova
O. G. Usalka
G. A. Belitsky
M. G. Yakubovskaya
K. I. Kirsanov
author_facet V. P. Maksimova
J. V. Makus
V. G. Popova
O. G. Usalka
G. A. Belitsky
M. G. Yakubovskaya
K. I. Kirsanov
author_sort V. P. Maksimova
collection DOAJ
description Background. DNA methylation is a crucial mechanism of epigenetic regulation of transcription. Disturbances in DNA methylation mechanism are associated with various malignancies such as acute myeloid leukaemia, breast cancer, prostate cancer, etc. Influencing the functional status of DNA methyltransferases (DNMTs) enzymes and TET family proteins (TETs), which regulate DNA methylation and demethylation, is the basis of epigenetic anticancer therapy approach. In this review, we have considered the challenges and prospects of nucleoside and non-nucleoside inhibitors of DNMTs as well as TETs inhibitors. The results of clinical trials on the efficacy of DNMTs inhibitors used individually and as part of combination chemotherapy conducted over the last 15 years are also evaluated. Material and Methods. Sources were searched in PubMed, ScienceDirect, Web of Science, eLibrary, CyberLeninka. More than 700 publications were used in the analysis, but the review included mainly works of the last 10 years. A number of articles published earlier than 2015 were used for historical reference. Results. The review provides information on current advances in the development and study of epigenetically active compounds whose action is aimed at the regulation of DNA methylation. Data on the in vitro and in vivo effects of agents considered for use in the therapy of various malignancies are presented. In addition, the data of clinical trials of the most promising epigenetic modulators are presented.
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spelling doaj-art-2ac159153f0b4d2aa0cb5e53074cca6a2025-08-20T03:56:41ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682024-09-0123412514010.21294/1814-4861-2024-23-4-125-1401259Approaches to anticancer therapy based on modulation of DNA methylationV. P. Maksimova0J. V. Makus1V. G. Popova2O. G. Usalka3G. A. Belitsky4M. G. Yakubovskaya5K. I. Kirsanov6N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia; National Research University Higher School of EconomicsN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia; RUDN UniversityN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia; Tufts UniversityN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of RussiaN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia; RUDN UniversityN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia; RUDN UniversityBackground. DNA methylation is a crucial mechanism of epigenetic regulation of transcription. Disturbances in DNA methylation mechanism are associated with various malignancies such as acute myeloid leukaemia, breast cancer, prostate cancer, etc. Influencing the functional status of DNA methyltransferases (DNMTs) enzymes and TET family proteins (TETs), which regulate DNA methylation and demethylation, is the basis of epigenetic anticancer therapy approach. In this review, we have considered the challenges and prospects of nucleoside and non-nucleoside inhibitors of DNMTs as well as TETs inhibitors. The results of clinical trials on the efficacy of DNMTs inhibitors used individually and as part of combination chemotherapy conducted over the last 15 years are also evaluated. Material and Methods. Sources were searched in PubMed, ScienceDirect, Web of Science, eLibrary, CyberLeninka. More than 700 publications were used in the analysis, but the review included mainly works of the last 10 years. A number of articles published earlier than 2015 were used for historical reference. Results. The review provides information on current advances in the development and study of epigenetically active compounds whose action is aimed at the regulation of DNA methylation. Data on the in vitro and in vivo effects of agents considered for use in the therapy of various malignancies are presented. In addition, the data of clinical trials of the most promising epigenetic modulators are presented.https://www.siboncoj.ru/jour/article/view/3199antitumour therapydna methylationdnmts inhibitorstets inhibitorsclinical trials
spellingShingle V. P. Maksimova
J. V. Makus
V. G. Popova
O. G. Usalka
G. A. Belitsky
M. G. Yakubovskaya
K. I. Kirsanov
Approaches to anticancer therapy based on modulation of DNA methylation
Сибирский онкологический журнал
antitumour therapy
dna methylation
dnmts inhibitors
tets inhibitors
clinical trials
title Approaches to anticancer therapy based on modulation of DNA methylation
title_full Approaches to anticancer therapy based on modulation of DNA methylation
title_fullStr Approaches to anticancer therapy based on modulation of DNA methylation
title_full_unstemmed Approaches to anticancer therapy based on modulation of DNA methylation
title_short Approaches to anticancer therapy based on modulation of DNA methylation
title_sort approaches to anticancer therapy based on modulation of dna methylation
topic antitumour therapy
dna methylation
dnmts inhibitors
tets inhibitors
clinical trials
url https://www.siboncoj.ru/jour/article/view/3199
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AT ogusalka approachestoanticancertherapybasedonmodulationofdnamethylation
AT gabelitsky approachestoanticancertherapybasedonmodulationofdnamethylation
AT mgyakubovskaya approachestoanticancertherapybasedonmodulationofdnamethylation
AT kikirsanov approachestoanticancertherapybasedonmodulationofdnamethylation