ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2021-3-182-192ssmu-4496Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESМолекулярно-генетические аспекты радиорезистентности рака предстательной железыMolecular genetic aspects of prostate cancer radioresistanceОмельчукЕ. П.OmelchukE. P.

 

 Россия, 344037, г. Ростов-на-Дону, ул. 14-я линия, 63 

 63, 14 Liniya Str., Rostov-on-Don, 344037, Russian Federation 

КутилинД. С.KutilinD. S.

 

 Россия, 344037, г. Ростов-на-Дону, ул. 14-я линия, 63 

 63, 14 Liniya Str., Rostov-on-Don, 344037, Russian Federation 

ДимитриадиС. Н.DimitriadiS. N.

 

 Россия, 344037, г. Ростов-на-Дону, ул. 14-я линия, 63 

 63, 14 Liniya Str., Rostov-on-Don, 344037, Russian Federation 

ГусареваМ. А.GusarevM. A.

 

 Россия, 344037, г. Ростов-на-Дону, ул. 14-я линия, 63 

 63, 14 Liniya Str., Rostov-on-Don, 344037, Russian Federation 

ТимошкинаН. Н.TimoshkinaN. N.

 

 Россия, 344037, г. Ростов-на-Дону, ул. 14-я линия, 63 

 63, 14 Liniya Str., Rostov-on-Don, 344037, Russian Federation 

Национальный медицинский исследовательский центр (НМИЦ) онкологииРоссияNational Medical Research Center for OncologyRussian Federation202121102021203182192Copyright © Омельчук Е.П., Кутилин Д.С., Димитриади С.Н., Гусарева М.А., Тимошкина Н.Н., 20212021Омельчук Е.П., Кутилин Д.С., Димитриади С.Н., Гусарева М.А., Тимошкина Н.Н.Omelchuk E.P., Kutilin D.S., Dimitriadi S.N., Gusarev M.A., Timoshkina N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/4496

Радиорезистентность рака предстательной железы представляет собой сложную терапевтическую проблему. После проведения лучевой терапии 22–69% больных раком предстательной железы сталкиваются с биохимическим рецидивом. Почти половина таких пациентов прогрессирует до клинического рецидива в течение 15 лет, а у трети наблюдается прогрессия до кастрационно-резистентного рака. Настоящий обзор посвящен анализу данных литературы о механизмах развития радиорезистентности в онкотрансформированных клетках предстательной железы. Осуществлен поиск литературных источников, опубликованных в базах eLibrary, PubMed, Scopus по ключевым словам: рак предстательной железы, радиорезистентность, маркеры. Всего найдено 568 иностранных и 178 отечественных работ, опубликованных в период 1975–2020 гг., из которых отобрано 77 статей, раскрывающих молекулярную основу радиорезистентности и вышедших в печать в 2001–2020 гг.Современные представления о происхождении устойчивых к радиации злокачественных клеток концентрируются на процессах, приводящих к усиленной репарации ДНК, активации антиапоптотических сигнальных путей, снижению уровня эндо- и экзогенных активных форм кислорода. Также немаловажную роль играют состояние микроокружения опухоли, аутофагия и эпителиально-мезенхимальный переход. Механизмы развития устойчивости к радиационному лечению на сегодняшний день объясняются наличием стволовых клеток опухоли, которые обусловливают генетическую гетерогенность и возможность ухода от воздействия терапии с помощью активации сигнальных путей канцерогенеза. Также опухоль может быть защищена от радиации гипоксической микросредой. Ввиду возникающей пластичности опухолевых стволовых клеток в ответ на лучевую терапию актуальным представляется поиск их маркеров с целью скрининга и идентификации радиорезистентного рака предстательной железы.

Radioresistance of prostate cancer is a complex therapeutic problem. Biochemical recurrence after radiation therapy occurs in 22–69% of patients with prostate cancer. Nearly half of these patients progress to a clinical relapse within 15 years, and a third progress to castration-resistant prostate cancer. This review analyzes literature data on radioresistance mechanisms in prostate cancer cells. We searched for literature published in eLibrary, PubMed, and Scopus databases by key words: prostate cancer, radioresistance, markers. In total, 568 foreign and 178 national articles published between 1975 and 2020 were found. Of these publications, 77 articles were selected (published in 2001–2020), which reveal the molecular basis of tumor radioresistance.Modern understanding of the origin of radioresistant cancer cells focuses on processes leading to enhanced DNA repair, activation of anti-apoptotic signaling pathways, and a decrease in the level of endogenous and exogenous reactive oxygen species. The state of a tumor microenvironment, autophagy, and epithelial-mesenchymal transition also play an important role in radioresistance. Currently, the mechanisms of resistance to radiation therapy are explained by the existence of tumor stem cells, which provide genetic heterogeneity and activation of carcinogenesis signaling pathways. The tumor can also be protected from radiation by a hypoxic microenvironment. Since cancer stem cells can acquire plasticity in response to radiation therapy, search for markers of radioresistance for screening and identification of radioresistant prostate cancer is relevant.

рак предстательной железырадиорезистентностьопухолевые стволовые клеткирепарация ДНКактивные формы кислородаэпителиально-мезенхимальный переходмикроокружениеаутофагияprostate cancerradioresistancecancer stem cellsDNA repairreactive oxygen speciesepithelialmesenchymal transitionmicroenvironmentautophagyИсследование выполнено в рамках государственного задания «Поиск молекулярно-генетических предикторов радиорезистентного рака предстательной железы и разработка персонифицированных терапевтических подходов».The study was carried out within the state assignment “Search for molecular genetic predictors of radioresistant prostate cancer and development of personalized treatment approaches”.ReferencesЗинькович М.С., Максимов А.Ю., Розенко Л.Я., Гусарева М.А., Карнаухова Е.А., Фаенсон А.В., Тимошкина Н.Н., Кутилин Д.С. Радиорезистентность как фактор эволюции лучевой терапии рака предстательной железы. Современные проблемы науки и образования. 2019; 2: 107. 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The authors declare that there are no conflicts of interest present.