antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-422Research ArticleОБЗОРЫREVIEWSМолекулярные мишени тамоксифена, отличные от эстрогеновых рецепторовTamoxifen Molecular Targets Different From Estrogen ReceptorsБогушТ. А.BogushT. A.noemail@neicon.ruДудкоЕ. А.DudkoE. A.noemail@neicon.ruБогушЕ. А.BogushE. A.noemail@neicon.ruПолоцкийБ. Е.PolotskyB. E.noemail@neicon.ruТюляндинС. А.TyulyandinS. A.noemail@neicon.ruДавыдовМ. И.DavydovM. I.noemail@neicon.ruРоссийский онкологический научный центр им. Н.Н. Блохина РАМН, МоскваРоссияN.N. Blokhin Russian Centre of Oncology, Russian Academy of Medical Sciences, MoscowRussian Federation201213052020571-25058Copyright © Богуш Т.А., Дудко Е.А., Богуш Е.А., Полоцкий Б.Е., Тюляндин С.А., Давыдов М.И., 20202020Богуш Т.А., Дудко Е.А., Богуш Е.А., Полоцкий Б.Е., Тюляндин С.А., Давыдов М.И.Bogush T.A., Dudko E.A., Bogush E.A., Polotsky B.E., Tyulyandin S.A., Davydov M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/422

Экспериментальные работы, раскрывающие всё новые и новые биологические эффекты воздействия тамоксифена на опухолевые клетки как экспрессирующие, так и неэкспрессирующие эстрогеновые рецепторы, позволяют по-новому взглянуть на, казалось бы, хорошо известный препарат. В обзоре описаны мишени тамоксифена, блокирование которых вызывает ингибирование роста опухолевых клеток и процесса ангиогенеза, стимулирование программированной смерти клеток (апоптоза, аутофагии и некроза), ингибирование механизма множественной лекарственной резистентности, торможение инвазии и метастазирования. Так как во всех случаях последствия взаимодействия тамоксифена с клетками являются прогностически благоприятными, как с точки зрения торможения роста опухоли и её метастазирования, так и с точки зрения чувствительности к лекарственной терапии, авторы рассматривают это как чрезвычайно важное «добавление» к антиэстрогенному эффекту тамоксифена. Приведены аргументы, которые позволяют считать стратегию длительной адъювантной терапии тамоксифеном, созданную ещё в 70 годах XX века профессором Craig V. Jordan для лечения рака молочной железы с позитивным статусом эстрогеновых рецепторов, применимой и для других опухолей. Это, прежде всего, описанный в последние годы факт экспрессии в солидных опухолях практически всех известных локализаций и гистологических типов эстрогеновых рецепторов бета, которые также являются мишенью тамоксифена. Авторы считают, что для полной реализации всех сторон биологической активности тамоксифена при длительной адъювантной терапии злокачественных новообразований разных локализаций, помимо оценки эстрогеновых рецепторов, необходим молекулярно-биологический отбор больных с учётом экспрессии других клеточных мишеней антиэстрогена.

Experimental studies showing ever new biological effects of tamoxifen on tumor cells, both expressing and nonexpressing estrogen receptors, are providing a novel conception of the drug, likely well known at present. The review describes tamoxifen targets, whose blocking induces inhibition of tumor cell growth and angiogenesis, stimulation of the programmed cell death (apoptosis, autophagia and necrosis), inhibition of multiple drug resistance mechanism and inhibition of invasion and metastasizing. In all the events, the results of the tamoxifen interaction with the cells are prognostically favourable from the viewpoint of both the inhibition of the tumor growth and metastasizing and the susceptibility to the medicinal therapy, that is considered by some authors as an extremely important addition to the tamoxifen antiestrogenic effect. The strategy of long-term tamoxifen adjuvant therapy of breast cancer with positive status of the estrogen reseptors was developed by Craig V. Jordan as far back as in the seventies of the XXth century, however there are arguments allowing to consider it also useful for the treatment of other tumors. First of all it is the fact desmbed lately in regard to expression of estrogen β-reseptors in solid tumors of practically all known localization and histological types, that are also the targets of tamoxifen. Apart from estimation of estrogen receptors, it is believed by some authors that molecular and biological choice of patients is necessary with an account of expression of other cell targets of antiestrogen for complete realization of all the aspects of tamoxifen biological activity in long-term adjuvant therapy of malignant tumors of various localization.

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