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РОЛЬ РЕЦЕПТОРОВ VEGFR В НЕОПЛАСТИЧЕСКОМ АНГИОГЕНЕЗЕ И ПЕРСПЕКТИВЫ ТЕРАПИИ ОПУХОЛЕЙ МОЗГА

https://doi.org/10.15690/vramn.v68i11.851

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Аннотация

Ввиду быстрой прогрессии, активного ангиогенеза, интенсивной инвазии и резистентности опухолей мозга, подходы к традиционной терапии остаются малоэффективными. В связи с этим активно изучают новые стратегии избирательного ингибирования критических стадий опухолевой прогрессии. Важнейшим фактором развития и роста солидных опухолей является неопластический ангиогенез, ключевую роль в регуляции которого играет фактор роста эндотелия сосудов (VEGF) и его рецептор 2-го типа (VEGFR2). Именно поэтому VEGFR2 как основной рецептор трансдукции проангиогенного сигнала рассматривают в качестве молекулярной мишени для антиангиогенной терапии. Ингибиторы VEGF и VEGFR2 подавляют пролиферацию, миграцию и выживаемость эндотелиоцитов, что приводит к регрессии сосудистой сети, снижению плотности и проницаемости сосудов; таким образом, замедляется рост опухоли. В настоящее время ряд ингибиторов VEGFR2 (рамуцирумаб, цедираниб) проходит клинические испытания. Несмотря на многообещающие результаты экспериментальных исследований, эффективность антиангиогенных препаратов в клинической практике оказывается существенно ниже. Это связано прежде всего с адаптивной устойчивостью малигнизированных клеток, которая включает активацию альтернативных проангиогенных путей, рекрутирование предшественников эндотелиальных клеток из костного мозга и увеличение вклада инвазивного роста. Учитывая многообразие существующих проангиогенных сигнальных механизмов, для повышения эффективности противоопухолевой терапии специфическое подавление функций VEGFR2 необходимо дополнять другими антиангиогенными препаратами (анти-VEGF, -PlGF, -HIF1α). Кроме того, мультитаргетная стратегия должна быть направлена на комбинированное подавление ангиогенеза, инвазии, метастазирования, пролиферации и выживаемости опухолевых клеток.

 

Об авторах

А. А. Корчагина
Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Российская Федерация
Россия


С. А. Шеин
ГНЦ социальной и судебной психиатрии им. В.П. Сербского, Москва, Российская Федерация
Россия


О. И. Гурина
ГНЦ социальной и судебной психиатрии им. В.П. Сербского, Москва, Российская Федерация
Россия


В. П. Чехонин
Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Российская Федерация ГНЦ социальной и судебной психиатрии им. В.П. Сербского, Москва, Российская Федерация
Россия


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Для цитирования:


Корчагина А.А., Шеин С.А., Гурина О.И., Чехонин В.П. РОЛЬ РЕЦЕПТОРОВ VEGFR В НЕОПЛАСТИЧЕСКОМ АНГИОГЕНЕЗЕ И ПЕРСПЕКТИВЫ ТЕРАПИИ ОПУХОЛЕЙ МОЗГА. Вестник Российской академии медицинских наук. 2013;68(11):104-114. https://doi.org/10.15690/vramn.v68i11.851

For citation:


Korchagina A.A., Shein S.A., Gurina O.I., Chekhonin V.P. VEGFRS IN NEOPLASTIC ANGIOGENESIS AND PROSPECTS FOR THERAPY ОF BRAIN TUMORS. Annals of the Russian academy of medical sciences. 2013;68(11):104-114. (In Russ.) https://doi.org/10.15690/vramn.v68i11.851

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