Genetic predictors of toxic effects of methotrexate in cancer patients

Abstract

Today, methotrexate (MTX) is used in combination with other medicines to treat a wide range of malignancies. De- spite 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 can - cer progression. Predicting the risk of MTX-induced toxicity is currently difficult due to the variability of pharmaco - kinetics 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 methylenetetra- hydrofolate 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.