akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2025.650akusherstvo-2515Research ArticleREVIEW ARTICLEНАУЧНЫЙ ОБЗОРMolecular mechanisms of glucose metabolism disorders in tumors of the female reproductive systemМолекулярные механизмы нарушения метаболизма глюкозы при опухолях женской репродуктивной системыhttps://orcid.org/0009-0001-8154-8187КовалеваЕ. Ю.KovalevaE. Yu.

Ковалева Екатерина Юрьевна

450008 Уфа, ул. Ленина, д. 3

Ekaterina Yu. Kovaleva

3 Lenin Str., Ufa 450008

https://orcid.org/0009-0000-2930-9958КантимироваР. Р.KantimirovaR. R.

Кантимирова Розалия Рустамовна

450008 Уфа, ул. Ленина, д. 3

Rozaliya R. Kantimirova

3 Lenin Str., Ufa 450008

https://orcid.org/0009-0008-2004-9537ГунинаТ. К.GuninaT. K.

Гунина Татьяна Константиновна

119048, Москва, ул. Трубецкая, д. 8, стр. 2

Tatyana K. Gunina

8 bldg. 2, Trubetskaya Str., Moscow 119048

https://orcid.org/0009-0009-6275-8355ВласенкоЕ. В.VlasenkoE. V.

Власенко Елизавета Владимировна

344022 Ростов-на-Дону, Нахичеванский пер., 29

Elizaveta V. Vlasenko

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022

https://orcid.org/0009-0004-8513-1030СалычинД. О.SalychinD. O.

Салычин Даниил Олегович

199034 Санкт-Петербург, Университетская наб., д. 7/9

Daniil O. Salychin

7/9 Universitetskaya Emb., Saint Petersburg 199034

https://orcid.org/0009-0000-8915-5604ХулаговаД. С.KhulagovaD. S.

Хулагова Дана Саидовна

350063 Краснодар, ул. Митрофана Седина, д. 4

Dana S. Khulagova

4 Mitrofana Sedina Str., Krasnodar 350063

https://orcid.org/0009-0003-1391-7993КочкинА.KochkinA.

Кочкин Алексей

248023 Калуга, ул. Степана Разина, д. 26

Aleksey Kochkin

26 Stepana Razina Str., Kaluga 248023

https://orcid.org/0009-0005-4877-2792МаматковаВ. А.MamatkovaV. A.

Маматкова Виктория Александровна

344022 Ростов-на-Дону, Нахичеванский пер., 29

Victoria A. Mamatkova

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022

https://orcid.org/0009-0006-9837-145XЖаковН. С.ZhakovN. S.

Жаков Николай Сергеевич

344022 Ростов-на-Дону, Нахичеванский пер., 29

Nikolai S. Zhakov

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022

https://orcid.org/0009-0004-7981-6957БезматерныхГ. К.BezmaternykhG. K.

Безматерных Глеб Константинович

344022 Ростов-на-Дону, Нахичеванский пер., 29

Gleb K. Bezmaternykh

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022

https://orcid.org/0009-0002-4638-8015ФоменкоЕ. Ю.FomenkoE. Yu.

Фоменко Елена Юрьевна

344029 Ростов-на-Дону, ул. Сержантова, д. 3

Elena Yu. Fomenko

3 Serzhantova Str., Rostov-on-Don 344029

razuvaeva.elena_98@mail.ruhttps://orcid.org/0009-0005-5196-9457МуллагалиеваА. А.MullagalievaA. A.

Муллагалиева Альфия Аликовна

420008, Казань, Кремлевская улица, д. 18, корп. 1

Alfiya A. Mullagalieva

18 bldg. 1, Kremlevskaya Str., Kazan 420008

https://orcid.org/0009-0005-7723-9954АлиФ. С.AliF. S.

Али Фатима Самир кызы

344022 Ростов-на-Дону, Нахичеванский пер., 29

Fatima S. Ali

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022

https://orcid.org/0009-0002-5273-2214ИмановаР. Н.ImanovaR. N.

Иманова Ругая Нафиз кызы

117513 Москва, ул. Островитянова, д. 1

Rugaya N. Imanova

1 Ostrovityanovа Str., Moscow, 117513

ФГБОУ ВО «Башкирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияBashkir State Medical University, Ministry of Health of the Russian FederationRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет)РоссияSechenov UniversityRussian FederationФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияRostov State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Санкт-Петербургский государственный университет»РоссияSaint Petersburg State UniversityRussian FederationФГБОУ ВО «Кубанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKuban State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Калужский государственный университет имени К.Э. Циолковского»РоссияTsiolkovsky Kaluga State UniversityRussian FederationГБУ РО «Детская городская поликлиника № 1»РоссияChildren's City Polyclinic No. 1Russian FederationФГАОУ ВО «Казанский (Приволжский) федеральный университет»РоссияKazan (Volga Region) Federal UniversityRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияPirogov Russian National Research Medical University, Ministry of Health of the Russian FederationRussian Federation20202807202500Online First2515Copyright © Kovaleva E.Y., Kantimirova R.R., Gunina T.K., Vlasenko E.V., Salychin D.O., Khulagova D.S., Kochkin A., Mamatkova V.A., Zhakov N.S., Bezmaternykh G.K., Fomenko E.Y., Mullagalieva A.A., Ali F.S., Imanova R.N., 20202020Ковалева Е.Ю., Кантимирова Р.Р., Гунина Т.К., Власенко Е.В., Салычин Д.О., Хулагова Д.С., Кочкин А., Маматкова В.А., Жаков Н.С., Безматерных Г.К., Фоменко Е.Ю., Муллагалиева А.А., Али Ф.С., Иманова Р.Н.Kovaleva E.Y., Kantimirova R.R., Gunina T.K., Vlasenko E.V., Salychin D.O., Khulagova D.S., Kochkin A., Mamatkova V.A., Zhakov N.S., Bezmaternykh G.K., Fomenko E.Y., Mullagalieva A.A., Ali F.S., Imanova R.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2515

Glucose metabolism plays a pivotal role in fueling the energetic and biosynthetic demands in rapidly proliferating cells. In gynecologic malignancies (GMs), including ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC), metabolic reprogramming occurs to support tumor growth, invasion, metastasis, and drug resistance. The current review provides a comprehensive analysis of the molecular mechanisms underlying glucose metabolism dysregulation in tumors of the female reproductive system, covering glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway (PPP). Special attention is paid to key enzymes such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), which are central to the Warburg effect. The review also addresses transcriptional regulators such as hypoxia-inducible factor 1-alpha (HIF-1α) and metabolic sensors like pyruvate dehydrogenase kinase 1 (PDK1) and isocitrate dehydrogenase 1 (IDH1) that play important roles in the adaptation of tumor cells to hypoxic conditions and in disease progression. Expression profiles of glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3), sodium glucose cotransporter 1 (SGLT1) and PPP enzymes – glucose-6-phosphate dehydrogenase (G6PD), transketolase-like 1 (TKTL1), are discussed in the context of redox homeostasis maintenance and the development of chemoresistance. Understanding these metabolic alterations opens avenues for identifying potential therapeutic targets and prognostic biomarkers. Incorporating molecular profiling into clinical practice may facilitate the development of personalized therapeutic strategies and improve the prognosis of patients with gynecologic cancers.

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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The authors declare that there are no conflicts of interest present.