akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2025.634akusherstvo-2442Research ArticleREVIEW ARTICLESНАУЧНЫЕ ОБЗОРЫNectin-4 significance in malignant neoplasms of the female reproductive system: a review of current dataЗначение нектина-4 при злокачественных новообразованиях женской репродуктивной системы: обзор современных данныхhttps://orcid.org/0009-0002-4790-2004РомановЕ. Г.RomanovE. G.

Романов Егор Геннадьевич

428015 Чебоксары, Московский проспект, д. 15

Egor G. Romanov

15 Moskovsky Avenue, Cheboksary 428015

romanov10a3@gmail.comhttps://orcid.org/0009-0006-0060-3604КокуринаК. А.KokurinaK. A.

Кокурина Ксения Алексеевна

428015 Чебоксары, Московский проспект, д. 15

Ksenia A. Kokurina

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0008-3124-7838ФедотоваА. А.FedotovaA. A.

Федотова Анжелика Андреевна

428015 Чебоксары, Московский проспект, д. 15

Anzhelika A. Fedotova

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0004-5568-5665МассолуЖ.Э.А.К.MassoluZh.E.A.K.

Массолу Жусту Эдуарду А. Камуени

428015 Чебоксары, Московский проспект, д. 15

Zhustu E.A.K. Massolu

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0002-5026-6977АндрееваА. И.AndreevaA. I.

Андреева Анастасия Игоревна

428015 Чебоксары, Московский проспект, д. 15

Anastasia I. Andreeva

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0001-0728-9404ХристофороваТ. С.KhristoforovaT. S.

Христофорова Татьяна Сергеевна 

428015 Чебоксары, Московский проспект, д. 15

Tatyana S. Khristoforova

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0000-3940-609XИвановаР. А.IvanovaR. A.

Иванова Регина Александровна

428015 Чебоксары, Московский проспект, д. 15

Regina A. Ivanova

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0006-1486-9323ТарасоваК. В.TarasovaK. V.

Тарасова Ксения Владимировна

428015 Чебоксары, Московский проспект, д. 15

Ksenia V. Tarasova

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0006-8115-0597ИвановМ. А.IvanovM. A.

Иванов Марат Андреевич 

428015 Чебоксары, Московский проспект, д. 15

Marat A. Ivanov

15 Moskovsky Avenue, Cheboksary 428015

https://orcid.org/0009-0009-1096-9388КлюкинаА. Э.KlyukinaA. E.

Клюкина Алина Эдуардовна 

390026 Рязань, Высоковольтная ул., д. 9

Alina E. Klyukina

9 Vysokovoltnaya Str., Ryazan 390026

https://orcid.org/0009-0008-3155-386XШарафанМ. А.SharafanM. A.

Шарафан Маргарита Алексеевна 

350063 Краснодар, ул. Митрофана Седина, д. 4

Margarita A. Sharafan

4 Mitrofana Sedina Str., Krasnodar 350063

https://orcid.org/0009-0003-2681-8265МедведькоЕ. В.MedvedkoE. V.

Медведько Елизавета Владимировна 

350063 Краснодар, ул. Митрофана Седина, д. 4

Elizaveta V. Medvedko

4 Mitrofana Sedina Str., Krasnodar 350063

https://orcid.org/0009-0006-5416-6577МоденоваМ. П.ModenovaM. P.

Моденова Мария Павловна 

350063 Краснодар, ул. Митрофана Седина, д. 4

Maria P. Modenova

4 Mitrofana Sedina Str., Krasnodar 350063

ФГБОУ ВО «Чувашский государственный университет имени И.Н. Ульянова»РоссияUlyanov Chuvash State UniversityRussian FederationФГБОУ ВО «Рязанский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov Ryazan State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Кубанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKuban State Medical University, Ministry of Health of the Russian FederationRussian Federation202519012026196923–941Copyright © Romanov E.G., Kokurina K.A., Fedotova A.A., Massolu Z., Andreeva A.I., Khristoforova T.S., Ivanova R.A., Tarasova K.V., Ivanov M.A., Klyukina A.E., Sharafan M.A., Medvedko E.V., Modenova M.P., 20262026Романов Е.Г., Кокурина К.А., Федотова А.А., Массолу Ж., Андреева А.И., Христофорова Т.С., Иванова Р.А., Тарасова К.В., Иванов М.А., Клюкина А.Э., Шарафан М.А., Медведько Е.В., Моденова М.П.Romanov E.G., Kokurina K.A., Fedotova A.A., Massolu Z., Andreeva A.I., Khristoforova T.S., Ivanova R.A., Tarasova K.V., Ivanov M.A., Klyukina A.E., Sharafan M.A., Medvedko E.V., Modenova M.P.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/2442Introduction

Introduction. Nectin-4, a cell adhesion molecule of the immunoglobulin superfamily (IgSF), has been extensively studied in oncological diseases. Nectin-4 is involved in the formation of intercellular connections and promotes tumor cell proliferation, migration and chemoresistance. Upregulated nectin-4 expression has been detected in various malignant neoplasms, including tumors of the female reproductive system – ovarian, endometrial, cervical cancer, as well as rare tumors of the vulva, vagina and fallopian tubes.

Aim

Aim: to summarize current data on nectin-4 role in the pathogenesis, diagnostics, prognosis and therapy of malignant tumors of the female reproductive system, and to assess the prospects for its clinical use in personalized medicine.

Materials and Methods

Materials and Methods. A search for relevant publications was conducted in the PubMed/MEDLINE, Scopus, Web of Science, Embase and eLibrary.ru databases beginning from January 2000 to December 2024. The inclusion criteria covered original and review articles devoted to nectin-4 in gynecological oncology. Key words in Russian and English, Boolean operators, and filtering by full-text, subject matter, and quality of research were used. From the 3955 identified publications, 65 were included in the review.

Results

Results. Nectin-4 expression is associated with enhanced tumor cell proliferation, migration, and chemoresistance, whereas its involvement in generating tight intercellular junctions promotes the development of chemoresistant spheroids. In ovarian cancer, upregulated levels of nectin-4 messenger RNA (mRNA) and serum protein demonstrated high diagnostic and prognostic significance, especially in combination with traditional markers such as cancer antigen 125 (CA-125). In endometrial cancer, nectin-4 expression correlates with a deficiency of the mismatch repair system (MMR genes) MSH2/MSH6 genes and lowered progression-free survival. In cervical carcinoma, nectin-4 is related to drug resistance, thereby positioning it as a promising target for novel treatment strategies. The latter using nanoquinacrine and antibody-drug conjugates (ADCs) such as 9MW2821 and ADRX-0706, are currently undergoing clinical trials. Additionally, nectin-4 has shown relevance in non-malignant reproductive disorders such as endometriosis and preeclampsia.

Conclusion

Conclusion. Nectin-4 demonstrates high clinical significance as a diagnostic and prognostic marker in gynecological malignancies. Its expression is associated with aggressive disease progression and drug resistance, especially in ovarian, endometrial and cervical cancers. Clinical trials with nectin-4-targeted drugs, including ADCs, are underway. Thus, nectin-4 represents a promising target for the development of personalized diagnostic and therapeutic strategies in gynecological oncology.

Введение

Введение. Нектин-4, молекула клеточной адгезии из суперсемейства иммуноглобулинов (англ. immunoglobulin superfamily, IgSF), активно изучается в контексте онкологических заболеваний. Нектин-4 принимает участие в формировании межклеточных соединений и способствует усилению пролиферации, миграции и устойчивости опухолевых клеток. Повышенная экспрессия нектина-4 выявлена при различных злокачественных новообразованиях, включая опухоли женской репродуктивной системы – рак яичников, эндометрия, шейки матки, а также редкие опухоли вульвы, влагалища и фаллопиевых труб.

Цель

Цель: обобщить современные данные о роли нектина-4 в патогенезе, диагностике, прогнозировании и терапии злокачественных опухолей женской репродуктивной системы, а также оценить перспективы его клинического применения в рамках персонализированной медицины.

Материалы и методы

Материалы и методы. Произведен поиск публикаций в базах данных PubMed/MEDLINE, Scopus, Web of Science, Embase и eLibrary.ru за период с января 2000 г. по декабрь 2024 г. Критерии включения охватывали оригинальные и обзорные статьи, посвященные нектину-4 в гинекологической онкологии. Использованы ключевые слова на русском и английском языках, булевы операторы, а также проведена фильтрация по полнотекстовости, тематике и качеству исследований. Из 3955 идентифицированных публикаций в обзор включены 65 работ.

Результаты

Результаты. Экспрессия нектина-4 ассоциирована с усиленной пролиферацией, миграцией и устойчивостью опухолевых клеток, а его участие в формировании плотных межклеточных соединений способствует развитию химиорезистентных сфероидов. При раке яичников повышенные уровни матричной РНК (мРНК) и сывороточного нектина-4 показали высокую диагностическую и прогностическую значимость, особенно в сочетании с традиционными маркерами, такими как раковый антиген 125 (англ. cancer antigen 125, CA-125). При раке эндометрия экспрессия нектина-4 коррелирует с дефицитом генов системы репарации несоответствий (англ. mismatch repair system genes, MMR genes) MSH2/MSH6 и снижением выживаемости без прогрессирования. При карциноме шейки матки нектин-4 связан с лекарственной устойчивостью, что делает его привлекательной мишенью для таргетной терапии. Рассматриваются новые подходы к лечению с использованием нанохинакрина и антитело-лекарственных конъюгатов (англ. antibodydrug conjugates, ADCs), таких как 9MW2821 и ADRX-0706, находящихся на стадии клинических испытаний. Также обсуждаются данные о роли нектина-4 при доброкачественных репродуктивных заболеваниях, таких как эндометриоз и преэклампсия.

Заключение

Заключение. Нектин-4 демонстрирует высокую клиническую значимость как диагностический и прогностический маркер при гинекологических злокачественных опухолях. Его экспрессия ассоциируется с агрессивным течением болезни и лекарственной устойчивостью, особенно при раке яичников, эндометрия и шейки матки. Ведутся клинические испытания таргетных препаратов, нацеленных на нектин-4, включая ADCs. Таким образом, нектин-4 представляет собой перспективную мишень для разработки персонализированных стратегий диагностики и лечения в онкогинекологии.

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