Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press1310.17650/2313-805X.2014.1.1.18-26REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИEstrogen-dependent signaling pathways and their role in the tumor progression: progress and perspectivesСигнальные пути, регулируемые эстрогенами, и их роль в опухолевой прогрессии: новые факты и направления поискаKrasil’nikovM. A.КрасильниковМ. А.
Russian Federation
krasilnikovm@main.crc.umos.ruShcherbakovA. M.ЩербаковА. М.
Russian Federation
ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, Москва150120141118260206201502062015Copyright ©; 2014, Krasil’nikov M.A., Shcherbakov A.M.Copyright ©; 2014, Красильников М.А., Щербаков А.М.2014Krasil’nikov M.A., Shcherbakov A.M.Красильников М.А., Щербаков А.М.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/13

Over the last forty years antiestrogen tamoxifen belongs to the most effective antitumor drugs widely used in the treatment of breast cancer, however, the efficiency of tamoxifen therapy is often limited by development of tumor hormonal resistance. The study of the mechanism of hormonal resistance led to the significant progress in the insight in signaling pathways respondent for the cancer cell growth in the absence of estrogen. In the review we have analyzed the recent data including our results obtained in the N. N. Blokhin RCRC, concerned with the study of the new aspects of hormonal resistance – the involvement of hypoxia-dependent HIF-1α / VEGF pathway, epithelial-mesenchymal transition and mTOR / AMPK in the formation of estrogen-independent phenotype. Some of the signaling proteins are considered as the potential targets for the therapy of the estrogen-resistant breast cancer.

Более сорока лет антиэстроген тамоксифен успешно применяется в терапии рака молочной железы, но основной проблемой в его применении до настоящего времени остается развитие у больных гормональной резистентности, существенно ограничивающей эффективность антиэстрогеновой терапии. За последние годы достигнут значительный прогресс в понимании механизмов формирования гормональной резистентности и выявлены новые молекулярные пути, поддерживающие рост опухоли в условиях «выключения» рецепторов эстрогенов. В обзоре проанализированы результаты исследований, в том числе выполненных в ФГБУ «РОНЦ им. Н. Н. Блохина» РАМН, посвященных новым аспектам этой тематики – активности сигнальных путей HIF-1α / VEGF, эпителиально-мезенхимального перехода и mTOR / AMPK; показано, как на молекулярном уровне формируется устойчивость опухоли к действию гормональных цитостатических препаратов. Некоторые из сигнальных белков рассмотрены в качестве показателей прогноза и / или перспективных мишеней таргетной терапии резистентных форм рака молочной железы.

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