Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press60910.17650/2313-805X-2023-10-4-47-60REVIEWОБЗОРНАЯ СТАТЬЯIntegration of phosphoinositide 3-kinase (PI3K) and transforming growth factor β1 (TGF-β1) signaling cascades: role in the therapeutic inefficiency of tamoxifenИнтеграция сигнальных каскадов фосфоинозитид-3-киназы (PI3K) и трансформирующего фактора роста β1 (TGF-β1): роль в реализации терапевтической неэффективности тамоксифенаhttps://orcid.org/0000-0002-0562-3878BabyshkinaN. N.БабышкинаН. Н.
Russian Federation

Nataliya N. Babyshkina.

5 Kooperativny Line, Tomsk 634009, Russia; 2 Moskovsky Trakt, Tomsk 634050

Бабышкина Наталия Николаевна.

634009 Томск, пер. Кооперативный, 5; 634050 Томск, Московский тракт, 2

nbabyshkina@mail.ruUzyanbaev I.  A.УзянбаевИ. А.
Russian Federation

2 Moskovsky Trakt, Tomsk 634050

634050 Томск, Московский тракт, 2

https://orcid.org/0000-0003-3009-2404Dronova T.  A.ДроноваТ. А.
Russian Federation

5 Kooperativny Line, Tomsk 634009

634009 Томск, пер. Кооперативный, 5

https://orcid.org/0000-0003-1526-9013CherdyntsevaN. V.ЧердынцеваН. В.
Russian Federation

5 Kooperativny Line, Tomsk 634009

634009 Томск, пер. Кооперативный, 5

Cancer Research Instituteof Tomsk National Research Medical Center of the Russian Academy of SciencesНаучно-исследовательский институт онкологии ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук»Siberian State Medical UniversityФГБОУ ВО «Сибирский государственный медицинский университет Минздрава России»1512202310447601307202315122023Copyright ©; 2023, Babyshkina N.N., Uzyanbaev  .A., Dronova  .A., Cherdyntseva N.V.Copyright ©; 2023, Бабышкина Н.Н., Узянбаев И.А., Дронова Т.А., Чердынцева Н.В.2023Babyshkina N.N., Uzyanbaev  .A., Dronova  .A., Cherdyntseva N.V.Бабышкина Н.Н., Узянбаев И.А., Дронова Т.А., Чердынцева Н.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/609

Growth factors signaling cascades and their interaction with the central regulatory targets of tumor cells and estrogens are considered as the main mechanisms of hormonal resistance in breast cancer. The integration  of the transforming growth factor β1 (TGF-β1) and PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway may result in the activation of proliferation and, as a result, the development of an in-effective response to therapy and disease progression. The review summarizes a systematic analysis of the literature data on the role of TGF-β1 signaling in the mechanisms of tamoxifen resistance to in the aspect of interaction  with the PI3K/Akt/mTOR. The interaction between the estrogen receptors α signaling and tamoxifen, the mechanisms of regulatory activation of TGF-β1 and PI3K/Akt/mTOR, as well as their contribution to the tamoxifen response are considered. The direct involvement of TGF-β1/PI3K in the mechanisms of tamoxifen resistance to determines the prospects for studying the effector of these cascades as molecular targets. The knowledge accumulated to date allows considering the TGF-β1/PI3K signaling pathway as a potential molecular tool for the search for effective strategies for blocking the resistance of tumor cells to tamoxifen.

Функционирование сигнальных каскадов факторов роста, их взаимодействие с центральными регуляторными мишенями опухолевых клеток и эстрогенами рассматриваются в качестве основных механизмов, опосредующих развитие гормональной резистентности при раке молочной железы. Результатом интеграции сигнального пути трансформирующего фактора роста β1 (TGF-β1) и PI3K (фосфоинозитид-3-киназа)/Akt (протеинкиназа B)/mTOR (мишень рапамицина млекопитающих) может являться активация пролиферативных процессов в клетках молочной железы и, как следствие, неэффективный ответ на терапию и прогрессирование заболевания. В обзоре представлен систематический анализ данных литературы, посвященной роли TGF-β1-сигнального пути в механизмах резистентности к тамоксифену в аспекте взаимодействия с каскадом PI3K/Akt/mTOR. Рассмотрены особенности взаимодействия сигнального пути рецепторов эстрогенов α, механизмы регуляторной активации TGF-β1 и PI3K/Akt/mTOR, а также их вклад в реализацию ответа на тамоксифен. Непосредственное вовлечение TGF-β1/PI3K в развитие устойчивости к данному препарату определяет перспективы изучения белков-эффекторов этих каскадов в качестве молекулярных мишеней. Накопленные к настоящему времени данные позволяют рассматривать сигнальный путь TGF-β1/PI3K как потенциальный молекулярный инструмент для поиска эффективных стратегий блокирования резистентности опухолевых клеток к тамоксифену.

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