Целевая терапия феминизированной природы рака предстательной железы: изучение эстрогензависимой метаболической перепрограммировки и ее терапевтического вмешательства: нарративный обзор

Рак предстательной железы (РПЖ) традиционно рассматривается как андроген-зависимое злокачественное новообразование. Однако накапливающиеся данные подчеркивают ключевую роль эстрогенов в его инициации, прогрессии и резистентности к терапии. Данный обзор устанавливает, что РПЖ обладает внутренней эстрогеновой зависимостью за счет интраопухолевой ароматизации, что позволяет рассматривать его в спектре эстроген-зависимых новообразований. Путем интегративного молекулярного анализа мы демонстрируем, как эстрогены регулируют метаболическую перепрограммировку, смещая опухоли предстательной железы к усиленному окислению липидов и захвату глюкозы признакам глюколипотоксичности. Механистически эстрогеновая сигнализация, преимущественно через путь PI3K/AKT, способствует повышенной экспрессии карнитинпальмитоилтрансферазы-1 и транспортера глюкозы-1, что запускает метаболическую бурю, характеризующуюся окислительным стрессом, митохондриальной дисфункцией и хроническим воспалительным сигналингом. Эта метаболическая адаптация позволяет опухолевым клеткам выживать независимо от андрогенов, создавая критическую уязвимость, которую игнорируют традиционные методы андроген-таргетной терапии. Наши выводы требуют пересмотра классификации и лечения РПЖ, предлагая новый терапевтический подход, нацеленный на ось «эстроген–метаболизм». Мы предлагаем точечную стратегию, включающую ингибирование ароматазы, блокаду эстрогеновых рецепторов и модуляцию метаболического стресса для борьбы с кастрационно-резистентной формой заболевания. Признание РПЖ как эстроген-зависимой метаболически адаптивной злокачественности изменяет его клиническое понимание и терапевтический подход, требуя срочного пересмотра существующих онкологических парадигм.

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