РНК-секвенирование и клеточные модели вирус-ассоциированного рака (обзор)

Обобщены результаты исследований, опирающихся на применение технологий транскриптомного анализа к современным клеточным модельным системам рака, ассоциированного с вирусом папилломы человека — ВПЧ (рака шейки матки, опухолей головы и шеи). Рассматривается многообразие трехмерных моделей рака, таких как сфероиды, органоиды (органотипические культуры), экспланты, мышиные ксенографты. Особое внимание уделено использованию биоматериала пациентов для получения временных культур первичных опухолевых клеток, а также созданию многокомпонентных (гетероклеточных) систем, включающих наравне с опухолевым компонентом элементы его микроокружения. Обсуждается ряд уникальных биологических свойств ВПЧ-индуцированных опухолей, которые делают получение клеточных моделей весьма незаурядной задачей.

Для каждого варианта модельных систем приведены новейшие обнаружения в области молекулярных механизмов возникновения и прогрессии ВПЧ-зависимого рака, сделанные с помощью РНК-секвенирования. Эти обнаружения рассматриваются в прикладном аспекте — с точки зрения открывающихся возможностей для доклинического тестирования новых препаратов, персонализированной диагностики и подбора индивидуальных, наиболее эффективных схем лечения. Рассмотрены вопросы формирования лекарственной устойчивости, молекулярно-клеточной гетерогенности, эпигенетического перепрограммирования, роли стромального микроокружения. Акцентируются проблемы, связанные с ограничениями применимости той или иной модельной системы. Отмечаются направления, по которым наблюдается существенное отставание омиксных исследований по вирус-ассоциированному раку в сравнении с другими типами онкопатологий, и возможные причины этого отставания. Обозначены также перспективы будущего развития модельных систем ВПЧ-ассоциированных опухолей в области высокотехнологичной тканевой инженерии, в частности применение биопечати и микрофлюидных биочипов. Сочетание данных технологий с методами полногеномного профилирования позволит существенно увеличить трансляционный потенциал описываемых модельных клеточных систем.

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