actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2021-6.4.3actabiomedica-2971Research ArticleГЕНЕТИКА, ПРОТЕОМИКА И МЕТАБОЛОМИКАGENETICS, PROTEOMICS AND METABOLOMICSГенетические основы кардиотоксичности антрациклинов: обзор литературыGenetic basis of anthracyclines cardiotoxicity: Literature reviewhttps://orcid.org/0000-0002-4824-2418СиницкийМ. Ю.SinitskyM. Yu.

 кандидат биологических наук, старший научный сотрудник лаборатории геномной медицины

650002, г. Кемерово, Сосновый бульвар, 6, Россия

 Cand. Sc. (Biol.), Senior Researcher at the Laboratory of Genomic Medicine 

Sosnoviy blvd 6, 650002, Kemerovo, Russian Federation 

sinitsky.maxim@gmail.comhttps://orcid.org/0000-0002-4467-8732ЦепокинаА. В.TsepokinaA. V.

 младший научный сотрудник лаборатории геномной медицины

650002, г. Кемерово, Сосновый бульвар, 6, Россия

 Junior Research Officer at the Laboratory of Genomic Medicine 

Sosnoviy blvd 6, 650002, Kemerovo, Russian Federation 

cepoav1991@gmail.comhttps://orcid.org/0000-0002-9714-4080ХуторнаяМ. В.KhutornayaM. V.

младший научный сотрудник лаборатории геномной медицины

650002, г. Кемерово, Сосновый бульвар, 6, Россия

 Junior Research Officer at the Laboratory of Genomic Medicine 

Sosnoviy blvd 6, 650002, Kemerovo, Russian Federation 

masha_hut@mail.ruhttps://orcid.org/0000-0002-3002-2863ПонасенкоА. В.PonasenkoA. V.

кандидат медицинских наук, заведующая лабораторией геномной медицины

650002, г. Кемерово, Сосновый бульвар, 6, Россия

 Cand. Sc. (Med.), Head of the Laboratory Genomic Medicine 

Sosnoviy blvd 6, 650002, Kemerovo, Russian Federation 

ponaav@kemcardio.ruhttps://orcid.org/0000-0002-0963-4793СуминА. Н.SuminA. N.

 доктор медицинских наук, заведующий лабораторией коморбидности при сердечно-сосудистых заболеваниях

650002, г. Кемерово, Сосновый бульвар, 6, Россия

 Dr. Sc. (Med.), Head of the Laboratory of Comorbidity in Cardiovascular Diseases 

 Sosnoviy blvd 6, 650002, Kemerovo, Russian Federation 

sumian@kemcardio.ruФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»Research Institute for Complex Issues of Cardiovascular Diseases202112102021642738Copyright © Синицкий М.Ю., Цепокина А.В., Хуторная М.В., Понасенко А.В., Сумин А.Н., 20212021Синицкий М.Ю., Цепокина А.В., Хуторная М.В., Понасенко А.В., Сумин А.Н.Sinitsky M.Y., Tsepokina A.V., Khutornaya M.V., Ponasenko A.V., Sumin A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/2971

Целью настоящего обзора стала систематизация данных о молекулярногенетических маркерах повышенного риска развития кардиотоксических эффектов, а также поиск рисковых и протективных вариантов кандидатных генов. На сегодняшний день терапия злокачественных новообразований основана на применении антрациклинов – препаратов цитостатического механизма действия. Наряду со своей эффективностью, данные препараты могут оказывать кардиотоксическое действие на кардиомиоциты за счёт увеличения количества активных форм кислорода и нарушения биогенеза митохондрий. Патологические нарушения приводят к повышению риска развития дисфункции миокарда и ряда других патологий сердечно-сосудистой системы у пациентов, получающих химиотерапию с использованием антрациклинов. Кардиотоксическое действие антрациклинов приводит к развитию кардиомиопатии, сердечной недостаточности, инфаркта миокарда и тромбоза. Раннее выявление кардиотоксических повреждений даёт возможность для изменений в схеме химиотерапии, которые могли бы снизить негативные эффекты применяемых препаратов. Известно, что риск развития кардиотоксических повреждений миокарда генетически детерминирован и контролируется более чем 80 генами. Данный обзор посвящён описанию основных молекул, таких как АТФ-связывающие кассетные транспортёры и транспортёры растворенных веществ (SLC транспортёров), карбонилредуктазы, антиоксидантной защиты, метаболизма ксенобиотиков и железа. Кроме того, отдельное внимание уделяется изучению эпигенетической и посттрансляционной регуляции. Имеющиеся данные отличаются некоторой противоречивостью, что может быть связано, в том числе, и с этническими особенностями изучаемых популяций и обусловливает необходимость более подробных исследований на различных этнических группах, а также необходимость изучения межгенных взаимодействий между потенциальными генами-кандидатами и эпигенетического регулирования. Таким образом, понимание вклада генетического полиморфизма поможет оценивать индивидуальные риски развития сердечно-сосудистой патологии у пациентов с различными видами онкологических заболеваний, а также снизить риск повреждения миокарда за счёт разработки индивидуальных профилактических мероприятий и коррекции химиотерапии.

The purpose of this review was to systematize data on molecular genetic markers of increased risk of cardiotoxic effects, as well as to search for risk and protective variants of candidate genes. Today, the therapy of malignant neoplasms is based on the use of anthracyclines – drugs of the cytostatic mechanism of action. Along with their effectiveness, these drugs can have a cardiotoxic effect on cardiomyocytes by increasing the amount of reactive oxygen species and disrupting mitochondrial biogenesis. Pathological disorders lead to an increased risk of myocardial dysfunction and a number of other cardiovascular pathologies in patients receiving chemotherapy using anthracyclines. The cardiotoxic effect of anthracyclines leads to cardiomyopathy, heart failure, myocardial infarction, and thrombosis. Early detection of cardiotoxic damage leads to reducing the negative effects of these drugs due to changes in chemotherapy tactics. It is known that the risk of cardiotoxic myocardial damage is genetically determined and controlled by more than 80 genes. In this review, the description of basic molecules such as ATP-binding cassette transporters and solute carrier family (SLC transporters), carbonyl reductase, molecules of antioxidant defense, xenobiotic and iron metabolism was performed. In addition, a special attention is paid to the study of epigenetic and post-translational regulation. The available data are characterized by some inconsistency that may be explained by the ethnic differences of the studied populations. Thus, a more detailed research of various ethnic groups, gene-gene interactions between potential candidate genes and epigenetic regulation is necessary. Thus, understanding the contribution of genetic polymorphism to the development of cardiotoxicity will help to assess the individual risks of cardiovascular pathology in patients with various types of cancer, as well as reduce the risk of myocardial damage by developing individual preventive measures and correcting chemotherapy.

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The authors declare that there are no conflicts of interest present.