Генетические полиморфизмы как предикторы токсичности метотрексата: обзор литературы

Введение. Большим достижением в лечении высокоагрессивных неходжкинских лимфом и острого лимфобластного лейкоза стало включение в протоколы терапии высокодозного (1000–5000 мг/м2) метотрексата. Подобный подход позволил существенно повысить показатели многолетней выживаемости больных, но оказался сопряжен с токсичностью лечения, требующей проведения сопроводительной терапии. Поиск факторов, которые могли бы предопределить развитие токсичности, позволил выделить гены, участвующие в метаболизме (например, MTHFR) или транспорте (SLCO1B1) метотрексата. Дальнейший анализ метаболизма метотрексата, определение дополнительных генов, участвующих в элиминации этого препарата, позволят более эффективно профилактировать и лечить токсические осложнения, сопряженные с противоопухолевыми эффектами метотрексата.

Цель исследования – изучение генетических полиморфизмов ферментов, участвующих в метаболизме метотрексата, и ассоциированной с ними токсичности при лечении острого лимфобластного лейкоза и неходжкинских лимфом у детей.

Материалы и методы. Проведен анализ данных в специализированных медицинских базах PubMed, Scopus, Web of Science, Frontiers, Google Scholar с 2001 по 2024 г. Результаты. Основными предикторами токсичности при использовании высокодозного метотрексата являются полиморфизмы генов MTHFR, SLCO1B1 и ARID5B.

Заключение. Несмотря на противоречивые данные, представленные в литературе, следует принимать во внимание обнаруживаемые полиморфизмы при проведении лечения высокодозным метотрексатом и своевременно выполнять сопроводительную терапию, направленную на предотвращение выраженной токсичности.

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