Department of Fundamental Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; Laboratory of Pharmacology, National Scientific Center of Marine Biology, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russia.
Medical Center, Far Eastern Federal University, Vladivostok, Russia.
Int Rev Neurobiol. 2020;151:67-98. doi: 10.1016/bs.irn.2020.03.002. Epub 2020 May 13.
Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor in humans. The prognosis for patients with GBM is unfavorable and treatment is largely ineffective, where modern treatment regimens typically increase survival by 15 months. GBM relapse and progression are associated with cancer stem cells (CSCs). The present review provides a critical analysis of the primary reasons underlying the lack of effectiveness of modern CSC management methods. An emphasis is placed on the role of the blood-brain barrier in the development of treatment resistance. The existing methods for increasing the efficiency of antitumor genotoxic therapy are also described, and a strategy for personalized regulation of CSC based on post-genome technologies is suggested. The hypothesis that GBM cells employ a special mechanism for DNA repair based on their interactions with normal stem cells, is presented and the function of the tumor microenvironment in fulfilling the antitumor potential of normal stem cells is explained. Additionally, the mechanisms by which cancer stem cells regulate glioblastoma progression and recurrence are described based on novel biomedical technologies.
胶质母细胞瘤(GBM)是人类最具侵袭性的脑肿瘤之一。GBM 患者的预后不佳,治疗效果大多不佳,现代治疗方案通常只能将患者的生存时间延长 15 个月。GBM 的复发和进展与癌症干细胞(CSC)有关。本综述对现代 CSC 管理方法缺乏有效性的主要原因进行了批判性分析。重点介绍了血脑屏障在治疗耐药性发展中的作用。还描述了提高抗肿瘤遗传毒性治疗效率的现有方法,并提出了一种基于后基因组技术的 CSC 个体化调控策略。提出了 GBM 细胞基于与正常干细胞的相互作用而采用特殊的 DNA 修复机制的假设,并解释了肿瘤微环境在发挥正常干细胞抗肿瘤潜能方面的作用。此外,还基于新的生物医学技术描述了癌症干细胞调节胶质母细胞瘤进展和复发的机制。