Possibilities of Predicting Methotrexate-associated Toxicity in Oncohematology Based on Molecular Genetic Testing Methods
Zarui K. Simavonyan,
Timur T. Valiev,
Marina I. Savelyeva,
Sherzod P. Abdullaev,
Svetlana R. Varfolomeeva https://doi.org/10.15690/pf.v21i5.2810
Abstract
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.
Supporting agencies: Not specified.
About the Authors
Zarui K. Simavonyan
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Disclosure of interest:
Russian Federation
Zarui K. Simavonyan, MD
Moscow
Disclosure of interest:
Not declared.
Timur T. Valiev
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia;
Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia
Russian Federation
Disclosure of interest:
Russian Federation
Timur T. Valiev, MD, PhD
23, Kashirskoe Shosse, Moscow, 115478
Disclosure of interest:
Not declared.
Marina I. Savelyeva
Yaroslavl State Medical University of the Ministry of Health of Russia
Russian Federation
Disclosure of interest:
Russian Federation
Marina I. Savelyeva, MD
Yaroslavl
Disclosure of interest:
Not declared.
Sherzod P. Abdullaev
Russian Medical Academy of Continuous Professional Education, Ministry of Health of Russia
Russian Federation
Disclosure of interest:
Russian Federation
Sherzod P. Abdullaev, MD, PhD
Moscow
Disclosure of interest:
Not declared.
Svetlana R. Varfolomeeva
N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia
Russian Federation
Disclosure of interest:
Russian Federation
Svetlana R. Varfolomeeva, MD, PhD
Moscow
Disclosure of interest:
Not declared.
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Review
For citations:
Simavonyan Z.K., Valiev T.T., Savelyeva M.I., Abdullaev Sh.P., Varfolomeeva S.R. Possibilities of Predicting Methotrexate-associated Toxicity in Oncohematology Based on Molecular Genetic Testing Methods. Pediatric pharmacology. 2024;21(5):449-454. (In Russ.) https://doi.org/10.15690/pf.v21i5.2810
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