Молекулярные механизмы нарушения метаболизма глюкозы при опухолях женской репродуктивной системы

Метаболизм глюкозы играет ключевую роль в обеспечении энергетических и биосинтетических потребностей быстро пролиферирующих клеток. При гинекологических злокачественных новообразованиях (ЗНО), включая рак яичников (РЯ), рак эндометрия (РЭ) и рак шейки матки (РШМ), происходит метаболическое перепрограммирование, направленное на поддержание роста опухоли, инвазии, метастазирования и лекарственной устойчивости. В настоящем обзоре представлен анализ молекулярных механизмов нарушения метаболизма глюкозы в опухолях женской репродуктивной системы, охватывающий гликолиз, цикл трикарбоновых кислот (ТТК) и пентозофосфатный путь (англ. pentose phosphate pathway, PPP). Особое внимание уделено ключевым ферментам, таким как гексокиназа 2 (англ. hexokinase 2, HK2), пируваткиназа M2 (англ. pyruvate kinase M2, PKM2), лактатдегидрогеназа A (англ. lactate dehydrogenase A, LDHA) и 6-фосфофрукто-2-киназа (англ. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3, PFKFB3), участвующим в реализации эффекта Варбурга. Также рассматриваются регуляторы транскрипции – индуцируемый гипоксией фактор-1α (англ. hypoxia-inducible factor 1-alpha, HIF-1α) и метаболические сенсоры – пируватдегидрогеназная киназа 1 (англ. pyruvate dehydrogenase kinase 1, PDK1) и изоцитратдегидрогеназа 1 (англ. isocitrate dehydrogenase 1, IDH1), играющие важную роль в адаптации опухолевых клеток к условиям гипоксии и в прогрессировании болезни. Обсуждаются профили экспрессии белков-переносчиков глюкозы (англ. glucose transporter 1, GLUT1; glucose transporter 3, GLUT3), натрий-зависимого глюкозного котранспортера 1 (англ. sodium glucose cotransporter 1, SGLT1) и ферментов PPP – глюкозо-6-фосфатдегидрогеназы (англ. glucose-6-phosphate dehydrogenase, G6PD), транскетолаза-подобного фермента 1англ. (англ. transketolase-like 1, TKTL1), вовлеченных в поддержание окислительно-восстановительного гомеостаза и развитие химиорезистентности. Понимание этих метаболических изменений позволяет рассматривать их как потенциальные терапевтические мишени и прогностические биомаркеры. Включение молекулярного профилирования в клиническую практику может способствовать разработке персонализированных стратегий терапии и улучшению прогноза пациенток с гинекологическими опухолями.

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