Prospects for molecular profiling in bladder cancer stratification and treatment. A review

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Abstract

Modern trends in oncological care are based on the principles of precision medicine, which necessitates the identification of prognostic and predictive molecular genetic markers. The results of genomic profiling of bladder cancer (BC) represent a wide range of genes involved in carcinogenesis, but the functional significance and clinical potential of most of them have not been sufficiently studied. The aim of this study was to summarize modern scientific and practical data on the trends in precision medicine in the field of oncourology in BC. The materials for the study were domestic and foreign scientific databases, in particular the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) using the electronic resource PubMed (https://pubmed.ncbi.nlm.nih.gov/), eLIBRARY.RU (https://www.elibrary.ru/) and Google Scholar (https://scholar.google.ru/schhp?hl=ru), when searching by keywords: BC, urothelial carcinoma, NGS, molecular profiling, genes, FGFR3, TERT, PIK3CA, TP53, mutations, expression. An analytical review concerning clinical, pathomorphological and molecular genetic data on the problems of diagnosis and treatment of BC included reports on preclinical experimental and clinical studies, meta-analyses, systematic reviews, cohort randomized studies for the period 2002–2025. A number of studies have demonstrated the association of molecular genetic changes in genes encoding receptor and intracellular kinases (FGFR2/3, PIK3CA etc.) with early stages of BC carcinogenesis, provided that the multifactorial prognostic significance is variable, taking into account the availability of modern molecular-targeted drugs. In particular, a pan-FGFR inhibitor, erdafitinib, which has demonstrated its effectiveness, is currently approved for the treatment of common forms of BC. Taking into account the pathogenetic mechanisms, an important further prospect for the use of receptor and intracellular kinase inhibitors in BC is the development and introduction into clinical practice of highly selective systemic and locally delivered forms with the possibility of their use in clinically heterogeneous groups of patients, including those with early stages of the disease. In turn, alterations in genes responsible for DNA repair (TP53, etc.) are associated with an aggressive course of the disease and a corresponding less favorable prognosis. In this direction, the key point of application of personalized therapy is the development and use of agents capable of modulating the activity of proteins of the reparation system at various stages of carcinogenesis. Thus, the mutational and functional status of genes involved in key oncogenic and reparation pathways in BC plays an important role in the context of developing a prognostic model, and also serves as a predictive target for therapeutic intervention.

About the authors

Liudmila N. Lyubchenko

National Medical Research Radiological Centre; Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Centre

Author for correspondence.
Email: clingen@mail.ru
ORCID iD: 0000-0003-4775-3299
SPIN-code: 9589-9057

D. Sci. (Med.)

Russian Federation, Moscow; Moscow

Karina M. Сhernavina

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre

Email: clingen@mail.ru
ORCID iD: 0000-0001-8291-804X
SPIN-code: 1457-7046

Clinical Resident

Russian Federation, Moscow

Koryun A. Ghazaryan

Peoples' Friendship University of Russia named after Patrice Lumumba

Email: clingen@mail.ru
ORCID iD: 0009-0005-1614-7650

 Graduate Student

Russian Federation, Moscow

Ivan N. Zaborskiy

Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre

Email: clingen@mail.ru
ORCID iD: 0000-0001-5988-8268
SPIN-code: 2445-5967

Cand. Sci. (Med.)

Russian Federation, Obninsk

Oleg B. Karyakin

Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre

Email: clingen@mail.ru
ORCID iD: 0000-0002-6112-2840
SPIN-code: 1486-9379

D. Sci. (Med.), Prof.

Russian Federation, Obninsk

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».