Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC13010.15690/vramn.v68i11.851SHORT MESSAGESКРАТКИЕ СООБЩЕНИЯVEGFRS IN NEOPLASTIC ANGIOGENESIS AND PROSPECTS FOR THERAPY ОF BRAIN TUMORSРОЛЬ РЕЦЕПТОРОВ VEGFR В НЕОПЛАСТИЧЕСКОМ АНГИОГЕНЕЗЕ И ПЕРСПЕКТИВЫ ТЕРАПИИ ОПУХОЛЕЙ МОЗГАKorchaginaA. A.КорчагинаА. А.
Russian Federation

postgraduate of the Department of Medical nanobiotechnologies of N.I. Pirogov RRMU. Address: 1, Ostrovityanov Street, Moscow, RF, 117997, tel.: +7 (495) 434-13-01

avilis1@yandex.ruSheinS. A.ШеинС. А.
Russian Federation

MD, research scientist of the Laboratory of Neurochemistry of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62

atomos@rambler.ruGurinaO. I.ГуринаО. И.
Russian Federation

PhD, Head of the Laboratory of Neurochemistry of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62

olga672@yandex.ruChekhoninV. P.ЧехонинВ. П.
Russian Federation

PhD, professor, academician of RAMS, Head of the Department of Fundamental and applied neurobiology of FSBI “V.P. Serbskii SSC of social and forensic psychiatry”, Head of the Department of Medical nanobiotechnologies of N.I. Pirogov RRMU. Address: 23, Kropotkinskii per., Moscow, RF, 119034, tel.: +7 (495) 695-02-62

chekhoninnew@yandex.ruPirogov Russian National Research Medical University, Moscow, Russian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Российская ФедерацияSerbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian FederationГНЦ социальной и судебной психиатрии им. В.П. Сербского, Москва, Российская ФедерацияPirogov Russian National Research Medical University, Moscow, Russian Federation Serbsky State Scientific Center for Social and Forensic Psychiatry, Moscow, Russian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Российская Федерация ГНЦ социальной и судебной психиатрии им. В.П. Сербского, Москва, Российская Федерация121120136811Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук10411407082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/130

Glioblastoma (GBM) is the most common type of primary brain cancer that characterized by poor prognosis due to the rapid progression, active angiogenesis, enhanced tumor cell invasion and the emergence of resistance toward conventional therapy. In this connection, nowadays, new approaches for selective inhibition of crucial steps in tumor progression are actively developing. The key feature of tumor growth and development is angiogenesis. VEGF and its receptor VEGFR2 play the pivotal role in regulation of tumor vessel formation. Therefore, VEGFR2, as the main receptor of VEGF’s pro-angiogenic signal transducer, is a promising molecular target for anti-angiogenic therapy. There is evidence that inhibitors of VEGF and VEGFR2 reduce endothelial cell proliferation, migration and survival that lead to regression of vessel density and decrease vascular permeability, thereby slowing tumor growth. Currently, a number of VEGFR2 inhibitors are under clinical trials (ramucirumab, cediranib) and several were approved (sunitinib, sorafenib). Despite the promising results of preclinical studies, the efficacy of antiangiogenic drugs in the clinical practice is significantly lower, mainly, due to rapid adaptation of malignant cells that consists of alternative pro-angiogenic pathways activation, recruitment of endothelial progenitor cells from bone marrow and increasing of the invasive growth. Given the diversity of pro-angiogenic mechanisms, enhancement of the efficacy of tumor therapy could be achieved by specific inhibition of VEGFR2 functions that will be supplemented by other antiangiogenic drugs (anti-VEGF,-PlGF,-HIF1α). In addition, multitargeting therapy should focus on the combined inhibition of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells.

Ввиду быстрой прогрессии, активного ангиогенеза, интенсивной инвазии и резистентности опухолей мозга, подходы к традиционной терапии остаются малоэффективными. В связи с этим активно изучают новые стратегии избирательного ингибирования критических стадий опухолевой прогрессии. Важнейшим фактором развития и роста солидных опухолей является неопластический ангиогенез, ключевую роль в регуляции которого играет фактор роста эндотелия сосудов (VEGF) и его рецептор 2-го типа (VEGFR2). Именно поэтому VEGFR2 как основной рецептор трансдукции проангиогенного сигнала рассматривают в качестве молекулярной мишени для антиангиогенной терапии. Ингибиторы VEGF и VEGFR2 подавляют пролиферацию, миграцию и выживаемость эндотелиоцитов, что приводит к регрессии сосудистой сети, снижению плотности и проницаемости сосудов; таким образом, замедляется рост опухоли. В настоящее время ряд ингибиторов VEGFR2 (рамуцирумаб, цедираниб) проходит клинические испытания. Несмотря на многообещающие результаты экспериментальных исследований, эффективность антиангиогенных препаратов в клинической практике оказывается существенно ниже. Это связано прежде всего с адаптивной устойчивостью малигнизированных клеток, которая включает активацию альтернативных проангиогенных путей, рекрутирование предшественников эндотелиальных клеток из костного мозга и увеличение вклада инвазивного роста. Учитывая многообразие существующих проангиогенных сигнальных механизмов, для повышения эффективности противоопухолевой терапии специфическое подавление функций VEGFR2 необходимо дополнять другими антиангиогенными препаратами (анти-VEGF, -PlGF, -HIF1α). Кроме того, мультитаргетная стратегия должна быть направлена на комбинированное подавление ангиогенеза, инвазии, метастазирования, пролиферации и выживаемости опухолевых клеток.

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