High dose methotrexate in adult Egyptian patients with hematological malignancies: impact of ABCB1 3435C &gt; T rs1045642 and MTHFR 677C &gt; T rs1801133 polymorphisms on toxicities and delayed elimination

Ebid, Abdel-Hameed I. Mohammed; Hossam, Ahmed; Gammal, Mosaad M. El; Soror, Sameh H.; Mangoud, Nadia O. M.; Mahmoud, M. A.

doi:10.1080/1120009x.2021.2009723

Cited by 4 publications

(1 citation statement)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a study by Han et al [24] involving patients with various types of malignant hematological diseases, the association of 3435CC genotype at the rs1045642 variant of the ABCB1 gene with a higher risk of hematological toxicity at an MTX dose of 2.5-5 g/m 2 was determined. In contrast, another study group did not observe a significant association between the rs1045642 variant of the ABCB1 gene and various types of toxicity when taking high doses of MTX in patients with hematological malignancies [25]. However, they found that carriers of the 3435T allele of the ABCB1 gene had a 10-fold higher risk of delayed MTX elimination.…”

Section: Other Transporters Of Methotrexatementioning

confidence: 89%

Genetic Predictors of Toxic Effects of Methotrexate in Cancer Patients

Fishchuk,

Skavinska,

Ievseienkova

et al. 2024

Exp. oncol.

View full text Add to dashboard Cite

Today, methotrexate (MTX) is used in combination with other medicines to treat a wide range of malignancies. Despite its proven high efficacy, MTX often causes serious side effects, which may result in the need to reduce the dose of MTX or discontinue the drug altogether. This, in turn, can provoke the development of MTX resistance and cancer progression. Predicting the risk of MTX-induced toxicity is currently difficult due to the variability of pharmacokinetics and pharmacodynamics in different patients, so the scientific literature is intensively searching for potential biomarkers. Based on the data available in the current literature, we analyzed the relationship between variants in the genes encoding the key components of MTX intracellular metabolism and the MTX-induced side effects and drug response. According to the results of our work, the most studied variants are those of the SLC19A1 gene, which encodes the reduced folate carrier protein 1, and the MTHFR gene, which encodes the enzyme methylenetetrahydrofolate reductase. Studies of the effect of methylation of the promoter regions of genes on the therapeutic effect of MTX are also very promising. In conclusion, the study of molecular genetic markers of MTX toxicity is extremely relevant and necessary because it can help to avoid the effect of multidrug resistance and improve the quality of life and survival of patients.

show abstract

Section: Other Transporters Of Methotrexatementioning

confidence: 89%