Фармакологическая регуляция стволовых клеток глиобластомы: реальность и перспективы

Глиобластома представляет собой наиболее агрессивную первичную нейроэпителиальную опухоль центральной нервной системы, характеризующуюся исключительно неблагоприятным прогнозом. Несмотря на комплексный терапевтический подход, включающий максимально возможную хирургическую резекцию с последующей радио- и химиотерапией, клинический исход остается неудовлетворительным: медиана общей выживаемости пациентов не превышает 15 месяцев. Ключевым патогенетическим фактором, определяющим резистентность к терапии и неизбежное рецидивирование опухоли, является наличие в ее структуре популяции опухолевых стволовых клеток (ОСК). Обсуждается идея создания новой циторегуляторной стратегии лечения глиобластомы, основанной на протеом-персонализированном подборе молекулярных мишеней, включая подавление β-катенина в опухолевых стволовых клетках (ОСК) с применением препаратов, преодолевающих гематоэнцефалический барьер. Важным компонентом данной стратегии является регуляция микроокружения ОСК путем блокирования сигнальной оси CXCR4/CXCL12. Стратегия также включает подавление механизмов привлечения иммуносупрессивных клеток (T-регуляторных лимфоцитов и миелоидных супрессорных клеток) в опухолевый очаг, что способствует восстановлению эффективного противоопухолевого иммунного ответа. Декларируется идея создания высокотехнологичных лекарственных препаратов аутологических CD45⁺ клеток, реактивированных ex vivo, с использованием экзогенной ДНК или РНК, транслирующих воспалительный сигнал в микроокружение ОСК.

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