Андрогендепривационная терапия рака предстательной железы: от механизма действия, осложнений и проблем до будущих перспектив

Рак предстательной железы относится к числу наиболее распространенных злокачественных новообразований у мужчин, а прогрессирование заболевания во многом определяется устойчивой активацией сигнального пути андрогенного рецептора (АР). Андрогендепривационная терапия (АДТ), направленная на подавление синтеза андрогенов и активации АР, является стандартным методом лечения. К методам АДТ относят хирургическую кастрацию, назначение агонистов/антагонистов гонадотропин-рилизинг-гормона, антиандрогенов и ингибиторов синтеза андрогенов. Несмотря на первоначальную эффективность, длительная АДТ часто осложняется развитием кастрационно-резистентного рака предстательной железы (КРРПЖ) и мультисистемной токсичностью с вовлечением метаболической, сердечно-сосудистой и костной систем. КРРПЖ развивается вследствие реактивации АР за счет амплификации генов, мутаций, вариантов сплайсинга и перекрестного взаимодействия с онкогенными сигнальными путями. Современная интенсификация лечения предполагает сочетание АДТ с ингибиторами АР нового поколения, химиотерапией и иммунотерапией. Предиктивные биомаркеры, такие как АР вариант 7 и гомеобокс B13, способствуют стратификации пациентов и принятию индивидуализированных терапевтических решений. Целью обзора является обобщение роли АДТ в лечении рака предстательной железы с особым акцентом на метаболизм андрогенов, сигнальный путь АР, механизмы кастрационной резистентности, осложнения, связанные с АДТ, и новые терапевтические стратегии. На основе систематического поиска литературы в PubMed и Embase за 2018–2025 г обобщены современные данные о метаболизме андрогенов, сигнальном пути АР, механизмах КРРПЖ, осложнениях, связанных с АДТ, и новых терапевтических стратегиях, направленных на оптимизацию долгосрочных результатов лечения.

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