МОЛЕКУЛЯРНЫЙ ПАТОГЕНЕЗ И МАРКЕРЫ ПОЧЕЧНОКЛЕТОЧНОГО РАКА

DOI: https://doi.org/10.29296/24999490-2019-02-01

А.Н. Ширшова(1), У.А. Боярских(1), кандидат биологических наук, М.Л. Филипенко(1, 2), кандидат биологических наук, В.С. Покровский(3), доктор медицинских наук, профессор, Н.Е. Кушлинский(3), доктор медицинских наук, профессор, член-корреспондент РАН 1-ФГБУН «Институт химической биологии и фундаментальной медицины» СО РАН, Российская Федерация, 630090, Новосибирск, ул. Акад. Лаврентьева, д. 8; 2-ФГАОУ ВО «Новосибирский государственный университет», Российская Федерация, 630090, Новосибирск, ул. Пирогова, д. 2; 3-ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Российская Федерация, 115478, Москва, Каширское шоссе, д. 24 E-mail: arina.shirshova@gmail.com

В обзоре освещены современные данные о молекулярном патогенезе и потенциальных маркерах светлоклеточного почечноклеточного рака (ПКР), полученные в мультиомиксных исследованиях. Ключевыми молекулярными механизмами патогенеза ПКР являются потеря функций генов VHL, PBRM1, SETD2, BAP1, KDM5C и CDKN2A и активация каскада PI3K-AKT-mTOR. В 91% случаев спорадической светлоклеточной карциномы почки один из аллелей VHL утрачивается в результате делеций короткого плеча 3 хромосомы. Второй аллель VHL в 55% случаев инактивируется вследствие соматических мутаций. В результате в клетке активируется HIF1-зависимая транскрипция генов адаптации к гипоксии, в том числе VEGF-А. Утрата функций генов PBRM1, SETD2, BAP1 и KDM5C приводит к нарушению процессов реорганизации хроматина. Все гены, за исключением KDM5C, расположены вблизи гена VHL на 3 хромосоме. В результате инактивации CDKN2A нарушается контроль клеточного цикла. Патологическая активность каскада PI3K-AKT-mTOR сопровождается синтезом белков, способствующих делению, росту и выживанию клетки. Антиангиогенная и анти-mTOR-терапия является стандартом лечения метастатического рака почки. Объективно на терапию отвечают в среднем 40% пациентов. У большинства формируется вторичная резистентность через 1–1,5 года успешной терапии. Возможность предсказания эффективности терапии и прогнозирования течения заболевания делают актуальной задачу поиска молекулярных маркеров ПКР. На сегодняшний день ни один из перспективных маркеров, в том числе ключевые молекулы патогенеза ПКР и мишени таргетной терапии, не рекомендован для использования в клинической практике.
Ключевые слова: 
патогенез, таргетная терапия

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