Современные представления о молекулярных механизмах резистентности к таргетной aHTu-HER2 терапии рака молочной железы

В лекции обобщены современные данные о молекулярных и генетических механизмах резистентности к таргетной анти-НЕКЗ терапии рака молочной железы (РМЖ), которая, несмотря на объективные успехи, остается неоптимальной. Так, в течение первых двух лет после завершения комбинированного лечения у 10-15% больных развиваются локорегиональные рецидивы, а у 15-25% пациентов в течение первых 5 лет динамического наблюдения отмечается отдаленное метастазирование, что обусловлено лекарствен­ной устойчивостью.

В качестве основных механизмов резистентности рассмотрены нарушение связывания таргетных препа­ратов с НЕК2-рецептором, активирующие мутации в гене HER2, внутриопухолевая гетерогенность HER2, перекрестное взаимодействие между HER2 и рецепторами эстрогена, нарушение внутриклеточной переда­чи сигналов, а также роли гетеродимера HER2-HER3 и опухолевого микроокружения. Отдельное внимание уделено факторам, ограничивающим эффективность конъюгатов моноклональных антител с цитостатика­ми, которые на сегодняшний день являются предметом активного изучения.

Понимание механизмов резистентности к анти-HER2 терапии имеет ключевое значение для оптимизации стратегий лечения больных HER2-положительным РМЖ, включая разработку новых препаратов, предот­вращение резистентности на начальных этапах, а также персонализацию терапии для улучшения прогноза данной категории пациентов.

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