Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review
Methotrexate (MTX) is one of the main chemotherapeutic agents that has determined the high effectiveness of protocols for the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphomas. The reverse side of the high anti-tumor activity of MTX is the adverse reactions, which require accompany...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | Russian |
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IP Habib O.N.
2021-12-01
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| Series: | Современная онкология |
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| Online Access: | https://modernonco.orscience.ru/1815-1434/article/viewFile/79133/pdf |
| _version_ | 1811258312528756736 |
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| author | Timur T. Valiev Vera V. Semenova Anna Yu. Ikonnikova Alisa A. Petrova Tatiana S. Belysheva Tatiana V. Nasedkina |
| author_facet | Timur T. Valiev Vera V. Semenova Anna Yu. Ikonnikova Alisa A. Petrova Tatiana S. Belysheva Tatiana V. Nasedkina |
| author_sort | Timur T. Valiev |
| collection | DOAJ |
| description | Methotrexate (MTX) is one of the main chemotherapeutic agents that has determined the high effectiveness of protocols for the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphomas. The reverse side of the high anti-tumor activity of MTX is the adverse reactions, which require accompanying preventive therapy. But even modern accompanying therapy in some cases does not avoid severe toxicity from the skin and mucous membranes, nervous system, kidneys, liver. MTX pharmacokinetics exhibits significant individual variability, which may be a reflection of genetic variability. Numerous pharmacogenetic studies have evaluated the effect of polymorphism of various genes involved in MTX metabolism on MTX pharmacokinetics and the development of toxic manifestations in order to improve patient outcomes and decrease drug toxicity. This review presents impact of key metabolic MTX genes (ATIC, DHFR, GGH, FPGS, MTHFR, MTR, MTRR, TYMS) and transporter proteins genes (ABCB1, ABCG2, ABCC2, ABCC4, SLC19A1, SLCO1B1) in the development of MTX side effects. Polymorphic markers in SLCO1B1 gene have the most influence with MTX pharmacokinetic. |
| first_indexed | 2024-04-12T18:11:21Z |
| format | Article |
| id | doaj.art-a95e206a932e48b58218232e6a8b05d2 |
| institution | Directory Open Access Journal |
| issn | 1815-1434 1815-1442 |
| language | Russian |
| last_indexed | 2024-04-12T18:11:21Z |
| publishDate | 2021-12-01 |
| publisher | IP Habib O.N. |
| record_format | Article |
| series | Современная онкология |
| spelling | doaj.art-a95e206a932e48b58218232e6a8b05d22022-12-22T03:21:48ZrusIP Habib O.N.Современная онкология1815-14341815-14422021-12-0123462262710.26442/18151434.2021.4.20112779365Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A reviewTimur T. Valiev0https://orcid.org/0000-0002-1469-2365Vera V. Semenova1https://orcid.org/0000-0002-9705-1001Anna Yu. Ikonnikova2https://orcid.org/0000-0002-8434-5916Alisa A. Petrova3https://orcid.org/0000-0002-7536-5683Tatiana S. Belysheva4https://orcid.org/0000-0001-5911-553XTatiana V. Nasedkina5https://orcid.org/0000-0002-2642-4202Blokhin National Medical Research Center of OncologyBlokhin National Medical Research Center of OncologyEngelhardt Institute of Molecular BiologyEngelhardt Institute of Molecular BiologyBlokhin National Medical Research Center of OncologyEngelhardt Institute of Molecular BiologyMethotrexate (MTX) is one of the main chemotherapeutic agents that has determined the high effectiveness of protocols for the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphomas. The reverse side of the high anti-tumor activity of MTX is the adverse reactions, which require accompanying preventive therapy. But even modern accompanying therapy in some cases does not avoid severe toxicity from the skin and mucous membranes, nervous system, kidneys, liver. MTX pharmacokinetics exhibits significant individual variability, which may be a reflection of genetic variability. Numerous pharmacogenetic studies have evaluated the effect of polymorphism of various genes involved in MTX metabolism on MTX pharmacokinetics and the development of toxic manifestations in order to improve patient outcomes and decrease drug toxicity. This review presents impact of key metabolic MTX genes (ATIC, DHFR, GGH, FPGS, MTHFR, MTR, MTRR, TYMS) and transporter proteins genes (ABCB1, ABCG2, ABCC2, ABCC4, SLC19A1, SLCO1B1) in the development of MTX side effects. Polymorphic markers in SLCO1B1 gene have the most influence with MTX pharmacokinetic.https://modernonco.orscience.ru/1815-1434/article/viewFile/79133/pdfmethotrexatepharmacogeneticsgenetic polymorphismfolate cycleside effects |
| spellingShingle | Timur T. Valiev Vera V. Semenova Anna Yu. Ikonnikova Alisa A. Petrova Tatiana S. Belysheva Tatiana V. Nasedkina Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review Современная онкология methotrexate pharmacogenetics genetic polymorphism folate cycle side effects |
| title | Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review |
| title_full | Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review |
| title_fullStr | Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review |
| title_full_unstemmed | Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review |
| title_short | Role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors: A review |
| title_sort | role of pharmacogenetic factors in the development of side effects of methotrexate in the treatment of malignant tumors a review |
| topic | methotrexate pharmacogenetics genetic polymorphism folate cycle side effects |
| url | https://modernonco.orscience.ru/1815-1434/article/viewFile/79133/pdf |
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