ppharmПедиатрическая фармакологияPediatric pharmacology1727-57762500-3089Издательство «ПедиатрЪ»10.15690/pf.v21i5.2810ppharm-2528Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWВозможности прогнозирования метотрексат-ассоциированной токсичности в онкогематологии на основании методов молекулярно-генетического тестированияPossibilities of Predicting Methotrexate-associated Toxicity in Oncohematology Based on Molecular Genetic Testing Methodshttps://orcid.org/0009-0008-1361-0082СимавонянЗ. К.SimavonyanZarui K.

Симавонян Заруи Кайцаковна 

Москва

Zarui K. Simavonyan, MD

Moscow

zarui@inbox.ruhttps://orcid.org/0000-0002-1469-2365ВалиевТ. Т.ValievTimur T.

Валиев Тимур Теймуразович, доктор медицинских наук, заведующий отделением детской онкологии и гематологии (химиотерапия гемобластозов) № 1 ФГБУ НМИЦ онкологии им. Н.Н. Блохина Минздрава России

115478, Москва, Каширское шоссе, д. 23

Timur T. Valiev, MD, PhD

23, Kashirskoe Shosse, Moscow, 115478

timurvaliev@mail.ruhttps://orcid.org/0000-0002-2373-2250СавельеваМ. И.SavelyevaMarina I.

Савельева Марина Ивановна, д.м.н., профессор

Ярославль

Marina I. Savelyeva, MD

Yaroslavl 

marinasavelyeva@mail.ruhttps://orcid.org/0000-0001-9001-1499АбдуллаевШ. П.AbdullaevSherzod P.

Абдуллаев Шерзод Пардабоевич, к.м.н. 

Москва

Sherzod P. Abdullaev, MD, PhD

Moscow

abdullaevsp@gmail.comhttps://orcid.org/0000-0001-6131-1783ВарфоломееваС. Р.VarfolomeevaSvetlana R.

Варфоломеева Светлана Рафаэлевна, д.м.н., профессор 

Москва

Svetlana R. Varfolomeeva, MD, PhD

Moscow

s.varfolomeeva@ronc.ruНМИЦ онкологии им. Н.Н. БлохинаРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaRussian FederationНМИЦ онкологии им. Н.Н. Блохина; РМАНПОРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia; Russian Medical Academy of Continuous Professional Education, Ministry of Health of RussiaRussian FederationЯГМУРоссияYaroslavl State Medical University of the Ministry of Health of RussiaRussian FederationРМАНПОРоссияRussian Medical Academy of Continuous Professional Education, Ministry of Health of RussiaRussian Federation202420112024215449454Copyright © Симавонян З.К., Валиев Т.Т., Савельева М.И., Абдуллаев Ш.П., Варфоломеева С.Р., 20242024Симавонян З.К., Валиев Т.Т., Савельева М.И., Абдуллаев Ш.П., Варфоломеева С.Р.Simavonyan Z.K., Valiev T.T., Savelyeva M.I., Abdullaev S.P., Varfolomeeva S.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pedpharma.ru/jour/article/view/2528

Разработка высокоэффективных протоколов терапии острого лимфобластного лейкоза (ОЛЛ) и неходжкинских лимфом (НХЛ) шла по пути эскалации доз цитостатических агентов и совершенствования сопроводительной терапии. Метотрексат (MTX), применяемый в высоких дозах (1000–5000 мг/м2), кардинально изменил результаты лечения ОЛЛ и НХЛ у детей, повысив показатели выживаемости пациентов. Обратной стороной противоопухолевого эффекта MTX представляется его органная токсичность, в связи с чем разработка методов прогнозирования развития токсических эффектов MTX является важной научно-практической задачей. В последние годы генетические факторы организма больного рассматривают как одну из причин индивидуальной вариабельности фармакокинетических и фармакодинамических параметров MTX. Аномальная функция ферментов фолатного цикла, белков-транспортеров меторексата, обусловленная полиморфизмом генов, может влиять на эффективность и токсичность препарата. В настоящем обзоре обобщены и проанализированы известные генетические полиморфизмы, участвующие в метаболизме MTX. Представлены возможности прогнозирования токсичности, а также перспективы индивидуализации терапии с учетом результатов фармакогенетического тестирования.

The development of highly effective protocols for the treatment of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphomas (NHL) followed the path of escalation of doses of cytostatic agents and improvement of supportive care. Methotrexate (MTX), used in high doses (1000–5000 mg/m2), radically changed the results of treatment of ALL and NHL in children, increasing patient survival rates. The downside of the anti-tumor effect of MTX is its organ toxicity, and therefore the development of methods for predicting the development of toxic effects of MTX is an important scientific and practical task. In recent years, the genetic factors of the patient’s organism have been considered as one of the reasons for the individual variability of pharmacokinetic and pharmacodynamic parameters of MTX. Abnormal function of folate cycle enzymes, methotrexate transporter proteins, due to gene polymorphism, may affect the effectiveness and toxicity of the drug. This review summarizes and analyzes the known genetic polymorphisms involved in MTX metabolism. The possibilities of predicting toxicity, as well as the prospects for individualizing therapy, taking into account the results of pharmacogenetic testing, are presented.

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