Опухолевые стволовые клетки мультиформной глиобластомы

Мультиформная глиобластома IV степени злокачественности по классификации Всемирной организации здравоохранения является наиболее распространенной первичной опухолью головного мозга с медианой выживаемости примерно 15–25 мес после лечения. Опухоль после хирургического лечения часто рецидивирует и резистентна к химио- и лучевой терапии. Мультиформная глиобластома представляет собой высокодифференцированную гетерогенную клеточную популяцию, способную образовывать опухолевые стволовые клетки (ОСК), и подразделяется на 4 молекулярных подтипа: пронейральный, нейральный, классический и мезенхимальный. Несмотря на ряд успехов в изучении механизмов, приводящих к образованию наиболее злокачественных подтипов опухоли, не ясны.

Цель работы – обобщение современных сведений о роли и биологических особенностях ОСК в опухолевой прогрессии и патогенезе мультиформной глиобластомы. Способность ОСК к образованию ниш с клетками эндотелия и микроокружением объясняет их основные свойства: пластичность фенотипа, адгезию, выживание и резистентность к стандартному противоопухолевому лечению. Наличие аберрантных сигнальных путей (Notch, Hedgehog-Gli, Wnt/β-катенин, TGF-β/SMAD, PI3K/Akt/mTOR) как в самой опухоли, так и в популяции ОСК, дисрегуляция микроРНК (miR-21, miR-128, miR-326, miR-34a и др.), влияние эпителиально-мезенхимального перехода объясняют характерные биологические характеристики ОСК. При разработке препаратов, направленных против ОСК, нужно учитывать влияние проводимой терапии и на нормальные стволовые клетки. Найденные за последнее десятилетие регуляторные механизмы и маркеры могут служить основой для создания новых лекарственных препаратов таргетного действия при лечении мультиформных глиобластом.

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