Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press191410.17650/1726-9776-2025-21-3-170-189REVIEWSОБЗОРЫReview ArticlePersonalized approach to systemic treatment of bladder cancer: molecular and genetic markers and new therapeutic strategies (literature review)Персонализированный подход к системному лечению рака мочевого пузыря: молекулярно-генетические маркеры и новые терапевтические стратегии (обзор литературы)https://orcid.org/0000-0002-9157-3589LyubchenkoL. N.ЛюбченкоЛ. Н.
Russian Federation
koryun13@gmail.comhttps://orcid.org/0009-0005-1614-7650GhazaryanK. A.КазарянК. А.
Russian Federation
koryun13@gmail.comhttps://orcid.org/0000-0001-8291-804XChernavinaK. M.ЧернавинаК. М.
Russian Federation
koryun13@gmail.comhttps://orcid.org/0000-0001-5988-8268ZaborskiyI. N.ЗаборскийИ. Н.
Russian Federation
i.zaborskii@mail.ruhttps://orcid.org/0000-0002-6112-2840KаryakinO. B.КарякинО. Б.
Russian Federation
karyakin@mrrc.obninsk.ruhttps://orcid.org/0000-0001-8784-8415KaprinA. D.КапринА. Д.
Russian Federation
kaprin@mail.ruNational Medical Research Radiological Center, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииN.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, Ministry of Health of RussiaНаучно-исследовательский институт урологии и интервенционной радиологии им. Н. А. Лопаткина – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииPeoples’ Friendship University of Russia named after Patrice LumumbaФГАОУ ВО «Российский университет дружбы народов им. Патриса Лумумбы»P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of RussiaМосковский научно-исследовательский онкологический институт им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииA.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center, Ministry of Health of RussiaМедицинский радиологический научный центр им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России181220252131701890503202526082025Copyright ©; 2025, Lyubchenko L.N., Ghazaryan K.A., Chernavina K.M., Zaborskiy I.N., Kаryakin O.B., Kaprin A.D.Copyright ©; 2025, Любченко Л.Н., Казарян К.А., Чернавина К.М., Заборский И.Н., Карякин О.Б., Каприн А.Д.2025Lyubchenko L.N., Ghazaryan K.A., Chernavina K.M., Zaborskiy I.N., Kаryakin O.B., Kaprin A.D.Любченко Л.Н., Казарян К.А., Чернавина К.М., Заборский И.Н., Карякин О.Б., Каприн А.Д.https://creativecommons.org/licenses/by/4.0https://oncourology.eco-vector.com/oncur/article/view/1914

Platinum-based cytotoxic chemotherapy is widely used in treatment of locally advanced and metastatic bladder cancer (BC) and is the therapy of choice in neoadjuvant treatment of muscle-invasive BC not only in the Russian Federation but worldwide. In the context of predicted significant increase in BC morbidity and mortality in the coming decades, the search for molecular and genetic markers and introduction of complex diagnostic models into clinical practice is relevant that allow for personalized approaches to patient treatment and prevention of BC in order to improve long-term treatment outcomes.

Molecular profiling of individual and tumor genomes allows for the identification of markers for assessing sensitivity to standard polychemotherapy regimens, as well as identifying targets for immune and targeted therapy of BC. A literature search conducted in international and domestic databases (NCBI (http://www.ncbi.nlm.nih.gov/), PubMed (https://pubmed.ncbi.nlm.nih.gov/), eLIBRARY.RU (https://www.elibrary.ru/), Google academy (https://scholar.google.ru/)) demonstrated that a wide range of molecular genetic changes are involved in the carcinogenesis of BC.

Based on a number of studies, it has been established that alterations in the ERBB2, FGFR3, PIK3CA, RB1, FANCC, DNAH, KDM6A, CDKN2A, MGAM2, RNF213, DDR (MLH1, MSH2/6, PMS1/2, BRCA1/2, CHEK1/2, PALB2, POLE, BLM, ATM, etc.) genes, as well as the expression levels of ERCC1, BRCA1, and CTR1 are associated with the sensitivity of BC to polychemotherapy. In turn, а number of molecular genetic markers are also associated with sensitivity to immunotherapy in BC, including PD-L1 expression, microsatellite instability, high tumor mutational load, APOBEC signatures, CDKN2A/CDKN2B deletions, PD-L1 promoter methylation, as well as alterations of the FGFR3, MDM2, and TP53 genes.

In addition, FGFR (fibroblast growth factor receptor) inhibitor – erdafitinib and conjugate of monoclonal antibodies with cytotoxic agents – enfortumab vedotin are recommended for the treatment of BC, having demonstrated their effectiveness in clinical trials.

Integration of molecular and genetic diagnostics into clinical oncological practice will improve the accuracy of patient stratification and optimize therapeutic decisions, reducing the risk of unjustified drug load and increasing the effectiveness of systemic treatment.

Цитотоксическая химиотерапия на основе препаратов платины по-прежнему является широко применяемой схемой лечения местно-распространенного и метастатического рака мочевого пузыря (РМП), а также терапией выбора при неоадъювантном лечении мышечно-инвазивного РМП не только в России, но и во всем мире. В условиях прогнозируемого значительного увеличения заболеваемости РМП и смертности от него в ближайшие десятилетия актуальны поиск молекулярно-генетических маркеров и внедрение в клиническую практику комплексных лечебно-диагностических моделей, позволяющих персонифицировать подходы к лечению и профилактике РМП в целях улучшения отдаленных результатов.

Молекулярное профилирование индивидуального и опухолевого геномов позволяет идентифицировать маркеры для оценки чувствительности к стандартным схемам полихимиотерапии, а также выявить мишени для иммунной и таргетной терапии РМП. Проведенный поиск литературы по международным и отечественным базам данных (NCBI (http://www.ncbi.nlm.nih.gov/), PubMed (https://pubmed.ncbi.nlm.nih.gov/), eLIBRARY.RU (https://www.elibrary.ru/), Google academy (https://scholar.google.ru/schhp?hl=ru)) продемонстрировал, что в канцерогенез РМП вовлечен широкий спектр молекулярно-генетических изменений.

На основании ряда работ установлено, что альтерации генов ERBB2, FGFR3, PIK3CA, RB1, FANCC, DNAH, KDM6A, CDKN2A, MGAM2, RNF213, DDR (MLH1, MSH2/6, PMS1/2, BRCA1/2, CHEK1/2, PALB2, POLE, BLM, ATM и др.), а также уровни экспрессии ERCC1, BRCA1 и CTR1 ассоциированы с чувствительностью РМП к полихимиотерапии. В свою очередь, для оценки прогнозирования ответа на иммунотерапию оценены и используются в клинической практике такие характеристики, как экспрессия PD-L1 и метилирование промотора PD-L1, статус микросателлитной нестабильности, опухолевая мутационная нагрузка, сигнатуры фермента модификации матричной РНК аполипопротеина B (APOBEC), делеции генов CDKN2A/CDKN2B, а также альтерации генов FGFR3, MDM2 и TP53.

В настоящее время для лечения РМП рекомендованы ингибитор FGFR (fibroblast growth factor receptor, рецептор фактора роста фибробластов) – эрдафитиниб, а также конъюгат моноклональных антител с цитотоксическими агентами – энфортумаб ведотин, продемонстрировавшие свою эффективность в клинических исследованиях.

Интеграция молекулярно-генетической диагностики в клиническую онкоурологическую практику позволит повысить точность стратификации пациентов и оптимизировать терапевтические решения, увеличивая эффективность системного лечения и снижая риск лекарственной нагрузки и токсических явлений.

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