oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-3-108-118oncotomsk-2590Research ArticleОБЗОРЫREVIEWSНеинвазивные методы молекулярной диагностики и клинического наблюдения и подходы к подбору персональной терапии при высокозлокачественных диффузных глиомах ствола мозгаNon-invasive methods of molecular diagnosis, clinical monitoring and approaches to the personalized therapy of diffuse midline gliomahttps://orcid.org/0000-0002-8150-7553ПетерсенЕ. В.PetersenE. V.

Петерсен Елена Владимировна - кандидат медицинских наук, заведующая лабораторией молекулярно-биологических и нейробиологических проблем и биоскрининга.

141701, Долгопрудный, Институтский переулок, 9

Researcher ID (WOS): L-2254-2013; Author ID (Scopus): 56496310300

Elena V. Petersen - MD,PhD, Head of the Laboratory of Molecular-Biological and Neurobiological Problems and Bioscreening, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

Researcher ID (WOS): L-2254-2013; Author ID (Scopus): 56496310300

https://orcid.org/0000-0002-9354-6824ЧудаковаД. А.ChudakovaD. A.

Чудакова Дарья Александровна - кандидат биологических наук, ведущий научный сотрудник лаборатории молекулярнобиологических и нейробиологических проблем и биоскрининга.

141701, Долгопрудный, Институтский переулок, 9

Daria A. Chudakova - PhD, Leading Researcher, Laboratory of Molecular-Biological and Neurobiological Problems and Bioscreening, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

https://orcid.org/0000-0003-2279-0157ЭрдынееваД. Б.ErdyneevaD. B.

Эрдынеева Даяна Батоевна - аспирант лаборатории молекулярно-биологических и нейробиологических проблем и биоскрининга.

141701, Долгопрудный, Институтский переулок, 9

Author ID (Scopus): 57218872794

Daiana B. Erdyneeva - MD, Postgraduate, Laboratory of Molecular-Biological and Neurobiological Problems and Bioscreening, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

Author ID (Scopus): 57218872794

daya-na@mail.ruhttps://orcid.org/0000-0002-1605-9088КалинкинА. A.KalinkinA. A.

Калинкин Александр Александрович - кандидат медицинских наук, нейрохирург, онкохирург.

115682, Москва, Ореховый бульвар, 28

Aleksandr A. Kalinkin - MD, PhD, neurosurgeon, oncosurgeon, Federal Scientific and Clinical Centre for Specialized Types of Medical Care and Medical Technologies, Federal Medical-Biological Agency of Russia.

28, Orekhovy bulvar, 115682, Moscow

https://orcid.org/0000-0002-2495-9772КларосР.ClarosR.

Кларос Роберто - студент 3-го курса Физтех-школы биологической и медицинской физики.

141701, Долгопрудный, Институтский переулок, 9

Roberto Claros - Student, Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

https://orcid.org/0000-0002-8184-7363ШабалинаЕ. Ю.ShabalinaE. Y.

Шабалина Евгения Юрьевна - аспирант, младший научный сотрудник лаборатории молекулярно-биологических и нейробиологических проблем и биоскрининга.

141701, Долгопрудный, Институтский переулок, 9

Researcher ID (WOS): AAB-2911-2019; Author ID (Scopus): 57212492791

Evgeniya Y. Shabalina - Postgraduate, Junior Researcher, Laboratory of Molecular-Biological and Neurobiological Problems and Bioscreening, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

Researcher ID (WOS): AAB-2911-2019; Author ID (Scopus): 57212492791

https://orcid.org/0000-0003-2582-1166ГудковД. А.GudkovD. A.

Гудков Денис Андреевич - кандидат химических наук, исполнительный директор Центра внедрения геномных технологий.

141701, Долгопрудный, Институтский переулок, 9

Denis A. Gudkov - PhD, Executive Director of the Center for the Implementation of Genomic Technologies, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

https://orcid.org/0000-0002-9309-1938МынбаевО. А.MynbaevО. A.

Мынбаев Оспан Абдрахманович - доктор медицинских наук, ведущий научный сотрудник лаборатории молекулярнобиологических и нейробиологических проблем и биоскрининга.

141701, Долгопрудный, Институтский переулок, 9

Researcher ID (WOS): K-5326-2013; Author ID (Scopus): 6602811094

Ospan A. Mynbaev - MD,DSc, Leading Researcher, Laboratory of Molecular-Biological and Neurobiological Problems and Bioscreening, Moscow Institute of Physics and Technology (National Research University).

9, Institutskiy per., 141701, Dolgoprudny

Researcher ID (WOS): K-5326-2013; Author ID (Scopus): 6602811094

https://orcid.org/0000-0002-3888-8004РешетовИ. В.ReshetovI. V.

Решетов Игорь Владимирович - доктор медицинских наук, заведующий кафедрой онкологии, радиотерапии и реконструктивной хирургии.

119991, Москва, ул. Трубецкая, 8/2

Igor V. Reshetov - MD, DSc, Head of the Department of Oncology, Radiotherapy and Reconstructive Surgery, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russia.

8/2, Trubetskaya St., 119991, Moscow

ФГАОУ ВО «Московский физико-технический институт (национальный исследовательский университет)»РоссияMoscow Institute of Physics and Technology (National Research University)Russian FederationФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий ФМБА России»РоссияFederal Scientific and Clinical Centre for Specialized Types of Medical Care and Medical Technologies, Federal Medical-Biological Agency of RussiaRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияI.M. Sechenov First Moscow State Medical University of the Ministry of Health of the RussiaRussian Federation202328062023223108118Copyright © Петерсен Е.В., Чудакова Д.А., Эрдынеева Д.Б., Калинкин А.A., Кларос Р., Шабалина Е.Ю., Гудков Д.А., Мынбаев О.А., Решетов И.В., 20232023Петерсен Е.В., Чудакова Д.А., Эрдынеева Д.Б., Калинкин А.A., Кларос Р., Шабалина Е.Ю., Гудков Д.А., Мынбаев О.А., Решетов И.В.Petersen E.V., Chudakova D.A., Erdyneeva D.B., Kalinkin A.A., Claros R., Shabalina E.Y., Gudkov D.A., Mynbaev О.A., Reshetov I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2590

Цель исследования - обобщение и анализ современных данных о неинвазивной молекулярной диагностике и соответствующих подходах к персонализированной терапии высокозлокачественных диффузных глиом ствола мозга (ДГСМ). Материал и методы. Поиск соответствующих источников производился в системах Google Scholar, Pubmed, Elsevier, Web of Science, Elibrary. В обзор включены публикации с 2011 по 2022 г. Из 102 найденных статей 59 были использованы для написания обзора. Результаты. В обзоре рассмотрены спектр соматических драйверных мутаций, присутствующих в опухолевых клетках ДГСМ, и их связь с чувствительностью опухолевых клеток к определенным видам терапии - фармакогенетический подход к подбору индивидуальных методов лечения (таргетная терапия). Обсуждаются новые методы таргетной терапии ДГСМ, находящиеся на стадии доклинической лабораторной разработки. Рассмотрены примеры использования 3D-клеточных культур для разработки таргетной терапии, в том числе с применением перфузионных систем. Описаны методы анализа жидкостной биопсии, позволяющие обнаружить опухоль-специфичные биомаркеры при неинвазивной диагностике ДГСМ, в том числе ряд методов, еще не протестированных в клинике. Приведен список опухоль-специфичных биомаркеров для диагностики, мониторинга и выбора таргетной терапии ДГСМ. В заключение обсуждается возможность внедрения данных методов в клинику, с представлением результатов нескольких клинических испытаний. Заключение. В онкологии новые методы молекулярной генетики, такие как анализ жидкостной биопсии, позволяют производить диагностику и мониторинг лечения в случаях, когда классические методы, требующие забора ткани, оказываются не применимы (к примеру, анализ генетически гетерогенных опухолей и опухолей хирургически недоступной локализации). К таким опухолям относится ДГСМ - первичная опухоль головного мозга, наиболее часто встречающаяся у детей. Имеющиеся данные подтверждают актуальность поиска новых специфических опухолевых биомаркеров, а также мишеней для таргетной терапии детских диффузных глиом.

The purpose of the study was to summarize and analyze modern data about non-invasive methods of molecular diagnosis and approaches to the personalized therapy of diffuse midline glioma (DMG). Material and Methods. The search and analysis of publications was carried out using Google Scholar, Pubmed, Elsevier, Web of Science, Elibrary systems. The review includes publications published from 2011 to 2022. Of the 102 articles found, 59 were used to write the review. Results. In this review, we discuss the spectrum of somatic driver mutations present in DMG tumor cells and their relationship with the sensitivity of tumor cells to certain types of therapy - a pharmacogenetic approach to the selection of individual treatments (targeted therapy). We provide examples of new methods of targeted therapy for DMG, which are currently at the stage of preclinical laboratory development. Also, we discuss examples of the use of 3D cell cultures for the development of targeted therapies, including the use of perfusion systems. The review describes the methods of analysis of liquid biopsy, which allow the detection of tumor-specific biomarkers in the non-invasive diagnosis of DMG, including a number of methods that have not yet been tested in the clinic. The following is a list of tumor-specific biomarkers for diagnosing, monitoring, and selecting targeted therapy for DMG. Finally, we discuss the possibility of implementing these methods in the clinic and present the results of several clinical trials. Conclusion. In oncology, new methods of molecular genetics, such as analysis of liquid biopsy, allow diagnosis and monitoring of treatment in cases where classical methods that require tissue sampling are not applicable (for example, the analysis of genetically heterogeneous tumors and tumors of surgically inaccessible localization). These tumors include DMG, a primary brain tumor most common in children. The available data confirm the relevance of the search for new specific tumor biomarkers, as well as targets for targeted therapy of the paediatric-type diffuse gliomas.

неинвазивная диагностикаопухоли центральной нервной системыдиффузные глиомы ствола мозгамолекулярно-генетические маркерыH3K27Mцифровая капельная ПЦРжидкостная биопсия3D-клеточные культурыперфузионная система клеточного культивированиябиобанкингnon-invasive diagnosticstumors of the central nervous systemdiffuse brainstem gliomasmolecular genetic markersH3K27Mdigital droplet PCRliquid biopsyex-vivo 3D cell cultures3D cell modelsbiobankingИсследование выполнено при финансовой поддержке РНФ гранты №21-15-00411 и РНФ №18-1500391. Исследование было выполнено при использовании ресурсов ЦКП МФТИ «Прикладная генетика» (грант №075-15-2021-684, госзадание 730000Ф.99.1.БВ10АА00006).The study was supported by the Russian Science Foundation (RSF) grant №21-15-00411 and grant №1815-00391. 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The authors declare that there are no conflicts of interest present.