surgoncoКреативная хирургия и онкологияCreative surgery and oncology2076-30932307-0501Башкирский государственный медицинский университет10.24060/2076-3093-2025-15-2-28-42surgonco-1085Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWSПовреждение и восстановление ДНК при глиобластоме: новые перспективы терапииDNA Damage and Repair in Glioblastoma: Emerging Therapeutic Perspectiveshttps://orcid.org/0000-0002-4965-0835ГареевИ. Ф.GareevI. F.

Гареев Ильгиз Фанилевич — к.м.н., старший научный сотрудник

Республика Башкортостан, Уфа; Москва 

Ilgiz F. Gareev — Cand. Sci. (Med.), Senior Researcher

Ufa; Moscow 

ilgiz_gareev@mail.ruhttps://orcid.org/0000-0002-6149-5460БейлерлиО. А.BeylerliO. A.

Бейлерли Озал Арзуман оглы — к.м.н., старший научный сотрудник

Республика Башкортостан, Уфа; Москва 

Ozal A. Beylerli — Cand. Sci. (Med.), Senior Researcher

Moscow 

https://orcid.org/0000-0002-7418-0222РумянцевС. А.RoumiantsevS. A.

Румянцев Сергей Александрович — д.м.н., профессор, член-корр. РАН

Москва 

Sergey A. Roumiantsev — Dr. Sci. (Med.), Prof., Corresponding Member of the Russian Academy of Sciences

Moscow 

Центральная научно-исследовательская лаборатория, Башкирский государственный медицинский университет ; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияCentral Research Laboratory, Bashkir State Medical University ; Pirogov Russian National Research Medical UniversityRussian FederationЦентральная научно-исследовательская лаборатория, Башкирский государственный медицинский университет ; Российский университет дружбы народов имени Патриса ЛумумбыРоссияCentral Research Laboratory, Bashkir State Medical University ; RUDN UniversityRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова ; Национальный медицинский исследовательский центр эндокринологииРоссияPirogov Russian National Research Medical University ; Endocrinology Research CentreRussian Federation202501072025152124138Copyright © Гареев И.Ф., Бейлерли О.А., Румянцев С.А., 20252025Гареев И.Ф., Бейлерли О.А., Румянцев С.А.Gareev I.F., Beylerli O.A., Roumiantsev S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surgonco.ru/jour/article/view/1085

Агрессивная и устойчивая к терапии природа глиобластомы делает ее одним из самых смертельных злокачественных новообразований у людей. Полная хирургическая резекция сложна, и для лечения оставшихся опухолевых клеток за пределами границы опухоли используется комбинация химио- и лучевой терапии, вызывающая повреждение ДНК опухолевой клетки и активирующая пути апоптоза. К сожалению, рецидивы являются обычным явлением и серьезным препятствием в лечении, часто встречающимся при более агрессивной и устойчивой к лечению глиобластоме. Известно, что репарация или восстановление ДНК и сигнальные пути повреждения ДНК имеют решающее значение для поддержания геномной стабильности. Дефекты путей репарации ДНК и сигнализации повреждения способствуют возникновению опухолей, но также делают опухолевые клетки уязвимыми к повреждению ДНК и зависимыми от остаточной репарационной и сигнальной активности. Понимание молекулярных элементов этих механизмов и выявление потенциальных терапевтических/фармакологических мишеней стали важнейшими задачами для эффективного лечения пациентов с глиобластомой. Доказано, что субпопуляция стволоподобных клеток, обозначенная как опухолевые стволовые клетки (ОСК) глиобластомы, ответственны не только за возникновение, поддержание и рецидив опухоли, они же поддерживают устойчивость к химиолучевой терапии из-за их повышенной способности к восстановлению ДНК. Более того, есть доказательства связей между углеводным метаболизмом и путями восстановления ДНК, что может открыть новые терапевтические возможности при глиобластоме. В данной работе обсуждаются современные стратегии изучения молекулярных механизмов целенаправленных путей репарации повреждения ДНК при глиобластоме. Мы суммируем недавний прогресс в наших знаниях о путях и факторах, вовлеченных в устранение повреждений ДНК, вызванных ионизирующим излучением и темозоломидом (TMZ) в частности. Наконец, мы представляем терапевтические стратегии, основанные на ингибиторах путей репарации ДНК, которые в настоящее время тестируются в преклинических или в клинических испытаниях.

Aggressive and therapy-resistant glioblastoma is among the most lethal malignant tumors in humans. Complete surgical resection is often unachievable; therefore, combination chemoradiotherapy is used to target tumor cells residual beyond the resection margin. This approach induces DNA damage in tumor cells and activates the apoptosis pathway. Unfortunately, recurrence remains a major clinical challenge, frequently manifesting as more aggressive and treatmentresistant glioblastoma phenotypes. The DNA repair and damage response (DDR) pathways are critical for maintaining genome stability. While defects in these mechanisms contribute to oncogenesis, they also make tumor cells vulnerable to DNA-damaging therapy, as the cells become dependent on residual repair capacity. It is of paramount importance to understand the molecular components of these mechanisms and to identify potential therapeutic/pharmacological targets for improving outcomes in glioblastoma patients. A subpopulation of stem-like cells, designated as glioblastoma cancer stem cells (CSCs), has been identified as a critical factor in the initiation, maintenance, and recurrence of tumors. These cells exhibit therapy resistance due to enhanced DNA repair capacity. In addition, emerging evidence suggests a link between carbohydrate metabolism and DNA repair pathways, thereby revealing novel therapeutic vulnerabilities in glioblastoma. This review examines current strategies targeting DNA repair mechanisms in glioblastoma. We present a synopsis of recent advancements in research concerning the mechanisms and factors involved in the elimination of DNA damage induced by ionizing radiation and temozolomide (TMZ). Furthermore, we explore the potential of DNA repair pathway inhibitors under investigation in preclinical and clinical trials.

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