Генетические основы кардиотоксичности антрациклинов: обзор литературы

Целью настоящего обзора стала систематизация данных о молекулярногенетических маркерах повышенного риска развития кардиотоксических эффектов, а также поиск рисковых и протективных вариантов кандидатных генов. На сегодняшний день терапия злокачественных новообразований основана на применении антрациклинов – препаратов цитостатического механизма действия. Наряду со своей эффективностью, данные препараты могут оказывать кардиотоксическое действие на кардиомиоциты за счёт увеличения количества активных форм кислорода и нарушения биогенеза митохондрий. Патологические нарушения приводят к повышению риска развития дисфункции миокарда и ряда других патологий сердечно-сосудистой системы у пациентов, получающих химиотерапию с использованием антрациклинов. Кардиотоксическое действие антрациклинов приводит к развитию кардиомиопатии, сердечной недостаточности, инфаркта миокарда и тромбоза. Раннее выявление кардиотоксических повреждений даёт возможность для изменений в схеме химиотерапии, которые могли бы снизить негативные эффекты применяемых препаратов. Известно, что риск развития кардиотоксических повреждений миокарда генетически детерминирован и контролируется более чем 80 генами. Данный обзор посвящён описанию основных молекул, таких как АТФ-связывающие кассетные транспортёры и транспортёры растворенных веществ (SLC транспортёров), карбонилредуктазы, антиоксидантной защиты, метаболизма ксенобиотиков и железа. Кроме того, отдельное внимание уделяется изучению эпигенетической и посттрансляционной регуляции. Имеющиеся данные отличаются некоторой противоречивостью, что может быть связано, в том числе, и с этническими особенностями изучаемых популяций и обусловливает необходимость более подробных исследований на различных этнических группах, а также необходимость изучения межгенных взаимодействий между потенциальными генами-кандидатами и эпигенетического регулирования. Таким образом, понимание вклада генетического полиморфизма поможет оценивать индивидуальные риски развития сердечно-сосудистой патологии у пациентов с различными видами онкологических заболеваний, а также снизить риск повреждения миокарда за счёт разработки индивидуальных профилактических мероприятий и коррекции химиотерапии.

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