medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-416medsovet-7987Research ArticleДЕТСКАЯ ОНКОЛОГИЯPEDIATRIC ONCOLOGYКлинические аспекты молекулярно-генетического тестирования в детской онкологииClinical impact of molecular genetic testing in pediatric oncologyhttps://orcid.org/0000-0002-2003-0982ДиникинаЮ. В.DinikinaYu. V.

Диникина Юлия Валерьевна - к.м.н., заведующая отделением химиотерапии онкогематологических заболеваний и трансплантации костного мозга для детей, заведующая научно-исследовательской лабораторией детской нейроиммуноонкологии.

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Yulia V. Dinikina - Cand. Sci. (Med.), Head of the Department of Chemotherapy of Oncohematological Diseases and Bone Marrow Transplantation for Children, Head of the Research Laboratory of Pediatric Neuroimmuno-Oncology, Almazov National Medical Research Centre.

2, Akkuratov St., St Petersburg, 197341

dinikinayulia@mail.ruhttps://orcid.org/0000-0003-4529-7891ИмянитовЕ. Н.ImyanitovE. N.

Имянитов Евгений Наумович - член-корр. РАН, д.м.н., профессор, заведующий научным отделом биологии опухолевого роста, лабораторией молекулярной онкологии.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Evgeny N. Imyanitov - Corr. Member RAS, Dr. Sci. (Med.), Professor, Head of the Scientific Department of Tumor Growth Biology, Laboratory of Molecular Oncology, Petrov National Medical Cancer Research Centre.

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758

evgeny@imyanitov.spb.ruhttps://orcid.org/0000-0001-9764-2090СуспицынЕ. Н.SuspitsinE. N.

Суспицын Евгений Николаевич - д.м.н., старший научный сотрудник лаборатории молекулярной онкологии отдела биологии опухолевого роста.

197758, Санкт-Петербург, пос. Песочный, ул. Ленинградская, д. 68

Evgeny N. Suspitsin - Dr. Sci. (Med.), Senior Researcher, Laboratory of Molecular Oncology, Department of Tumor Growth Biology, Petrov National Medical Cancer Research Centre.

68, Leningradskaya St., Pesochnyy Settlement, St Petersburg, 197758

evgeny.suspitsin@gmail.comhttps://orcid.org/0000-0002-8607-3635ЖелудковаО. Г.ZheludkovaO. G.

Желудкова Ольга Григорьевна - д.м.н., профессор.

119620, Москва, ул. Авиаторов, д. 38

Olga G. Zheludkova - Dr. Sci. (Med.), Professor, Voino-Yasenetsky Scientific and Practical Center for Specialized Medical Care.

38, Aviatorov St., Moscow, 119620

clelud@mail.ruhttps://orcid.org/0000-0003-4013-0785НикитинаИ. Л.NikitinaI. L.

Никитина Ирина Леоровна - д.м.н., профессор, заведующая научно-исследовательской лабораторией детской эндокринологии института эндокринологии.

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Irina L. Nikitina - Dr. Sci. (Med.), Professor, Head of the Research Laboratory of Pediatric Endocrinology, Institute of Endocrinology, Almazov National Medical Research Centre.

2, Akkuratov St., St Petersburg, 197341

nikitina0901@gmail.comhttps://orcid.org/0000-0002-7471-7181БелогуроваМ. Б.BelogurovaM. B.

Белогурова Маргарита Борисовна - д.м.н., профессор, ведущий научный сотрудник института гематологии.

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Margarita B. Belogurova - Dr. Sci. (Med.), Professor, Leading Researcher at the Institute of Hematology, Almazov National Medical Research Centre.

2, Akkuratov St., St Petersburg, 197341

deton.hospital31@inbox.ruНациональный медицинский исследовательский центр имени В.А. АлмазоваРоссияAlmazov National Medical Research CentreRussian FederationНациональный медицинский исследовательский центр онкологии имени Н.Н. ПетроваРоссияPetrov National Medical Cancer Research CentreRussian FederationНаучно-практический центр специализированной медицинской помощи имени В.Ф. Войно-ЯсенецкогоРоссияVoino-Yasenetsky Scientific and Practical Center for Specialized Medical CareRussian Federation202317012024022122128Copyright © Диникина Ю.В., Имянитов Е.Н., Суспицын Е.Н., Желудкова О.Г., Никитина И.Л., Белогурова М.Б., 20242024Диникина Ю.В., Имянитов Е.Н., Суспицын Е.Н., Желудкова О.Г., Никитина И.Л., Белогурова М.Б.Dinikina Y.V., Imyanitov E.N., Suspitsin E.N., Zheludkova O.G., Nikitina I.L., Belogurova M.B.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7987

Онкологические заболевания занимают лидирующие позиции в структуре детской смертности, несмотря на значительные успехи в их лечении. Летальность может быть обусловлена не только прогрессированием основного заболевания ввиду резистентности опухоли к проводимой терапии, но и лекарственно-индуцированной токсичностью, и инфекционными осложнениями. Использование новых диагностических технологий, способствующих выявлению клинически значимых молекулярно-генетических альтераций в опухоли, делает возможным индивидуальный подход к выбору терапии с целью повышения ее эффективности и снижения токсичности, а таже улучшения качества жизни пациентов и их семей в период проведения специфического лечения. Наиболее перспективными диагностическими тестами в указанном аспекте являются разновидности секвенирования нового поколения: широкопанельное таргетное, полноэкзомное и полногеномное секвенирование опухолевого материала и лейкоцитарной ДНК пациента. Несмотря на относительную редкость выявляемых патогенных генетических альтераций, ряд из них имеют прогностическую значимость, определяют чувствительность к противоопухолевому лечению, а также являются мишенями для проведения направленной терапии. При этом последняя при ряде нозологий демонстрирует преимущества по сравнению со стандартными методами лечения. Тем не менее применение противоопухолевых препаратов таргетного механизма действия в педиатрической популяции сопряжено с рядом ограничений по сравнению со взрослым населением. В первую очередь это обусловлено отсутствием утвержденных доз, режимов и показаний к применению для большей части новых лекарственных препаратов, рисками развития нежелательных явлений, а также их высокой стоимостью. В статье представлены актуальные вопросы клинического применения таргетной терапии в онкопедиатрии на основании данных молекулярно-генетической диагностики.

Despite remarkable progress in the management of pediatric oncological diseases they remain one of the leading causes of mortality. The disease progression due to tumor resistance, treatment-induced toxic effects and infections complications may contribute to the lethality. New diagnostic technologies facilitate the identification of clinically significant genetic alterations for individualization of therapy approach in order to increase its effectiveness, reduce associated toxicity and improve quality of life of patients and their families. The most promising diagnostic approach is based on next-generation sequencing and includes targeted-, whole exome- and genome sequencing of patients’ blood DNA and tumor tissue. Despite the low rate of detected pathogenic alterations, some of them have prognostic significance, determine sensitivity to anticancer agents and targeted therapy. Moreover, targeted therapy in some cancer types shows benefit over standard therapeutic options. The application of targeted therapy in pediatric patients poses more challenges than in adults. This is due to the absence of established doses, regimens and indications for targeted agents in pediatric clinical trials, risks of associated toxicity and its high cost. This paper summarizes the data on molecular genetic markers, which are potentially helpful in guiding therapy for cancer in children.

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