Анализ циркулирующей опухолевой ДНК и новые возможности использования анти-EGFR моноклональных антител у пациентов с метастатическим колоректальным раком

В настоящее время исследование биоптата опухолевой ткани с целью определения альтераций в генах RAS/BRAF, оценки статуса микросателлитной нестабильности, а также определения амплификации/гиперэкспрессии гена HER‑2/neu является золотым стандартом диагностики и позволяет осуществить выбор оптимальной молекулярно-направленной терапии при рассмотрении стратегий лечения пациентов с метастатическим колоректальным раком. Однако биопсия не позволяет в полной мере отразить существующую внутриопухолевую гетерогенность и клональную эволюцию опухолевых клеток, что, зачастую, может быть причиной терапевтических неудач. В последние годы жидкостная биопсия привлекает все большее внимание как дополнительный и потенциально альтернативный неинвазивный инструмент молекулярного профилирования опухоли. Оценка циркулирующей опухолевой ДНК позволяет отслеживать изменения генетического статуса опухоли, а также динамически измерять «бремя» болезни в режиме реального времени. Благодаря развитию технологий жидкостной биопсии появились новые многообещающие стратегии ведения пациентов с метастатическим колоректальным раком на поздних линиях терапии. Стандартный лекарственный арсенал у данной группы больных ограничен или повторным назначением ранее эффективной терапии или регорафенибом и комбинацией трифлуридин/типирацила с бевацизумабом, которые характеризуются ограниченной клинической активностью. Однако, благодаря открытию феномена NeoRAS wild-type истратегии rechallenge анти-EGFR моноклональных антител, основанных на изучении клональной селекции и эволюции опухолевых клеток, назначение ингибиторов эпидермального фактора роста в молекулярно-отобранной посредством жидкостной биопсии популяции сопровождается хорошей переносимостью и эффективностью. В настоящий момент продолжаются многочисленные клинические исследования, направленные на дальнейшее понимание механизмов резистентности опухоли и разработку новых научно обоснованных лечебных подходов с целью реализации концепции персонализированной медицины.

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