胶质母细胞瘤的现代治疗方法

N. S. Kuznetsova, S. Gurova, A. Goncharova, E. Zaikina, M. Gusareva, M. Zinkovich
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摘要

胶质母细胞瘤(GBM)是最恶性和最常见的原发性中枢神经系统肿瘤。在过去几年中,根据世界卫生组织(世卫组织)将其细分为原发性和继发性GBM的标准对GBM进行了分类和管理。目前认为,GBM起源于神经胶质细胞,具有弥漫性生长模式,但其病因和病理生理研究尚不充分。它在大脑中的快速进展和解剖位置往往限制了治疗干预的有效性。尽管科技进步,GBM仍然是一种无法治愈的疾病,中位生存期约为18个月。标准的治疗方案包括最大限度的安全切除肿瘤,然后是放疗和化疗,并没有提供令人满意的结果。更好地了解GBM的分子病理学及其相关的信号通路,为新诊断和复发肿瘤的新治疗开辟了可能性。使用能够抑制多个特定分子靶点的化合物的多靶点治疗方法是传统治疗的有希望的替代方法。目前,专家们正在研究诸如针对信号通路中断的小分子抑制剂、免疫疗法(包括检查点抑制剂)、溶瘤疫苗、CAR - t细胞疗法和药物输送系统等创新治疗方案。就创新方法而言,拟定靶向给药系统特别令人感兴趣,因为这种策略看起来最有希望,因为它能够提高标准药物和新测试药物的生物利用度和有效性。本文综述了创新治疗方法的临床前和临床研究结果及其优缺点。跨学科的方法有望结合这一领域的前沿研究成果,并为GBM患者提供新的有希望的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modern approaches to glioblastoma therapy
Glioblastoma (GBM) is the most malignant and the most common primary tumor of the central nervous system. During the last several years GBM has been classified and managed according to the World Health Organization (WHO) criteria which subdivide it into primary and secondary GBM. As it is suggested, GBM originates from glial cells and has a diffuse growth pattern, but its etiology and pathophysiology are poorly investigated up to date. Its rapid progression and anatomical location in the brain often limits the effectiveness of therapeutic interventions. Despite all scientific and technological advances, GBM remains an incurable disease with a median survival of approximately 18 months. Standard treatment options involving maximal safe resection of the tumor followed with radiotherapy and chemotherapy do not provide satisfactory Results.Better understanding of the molecular pathology of GBM and its associated signaling pathways has opened up possibilities for new treatments for newly diagnosed and relapsing tumors. A multitargeted therapeutic approach using compounds capable of inhibiting more than one specific molecular target is a promising alternative to conventional therapies.Currently, specialists study such innovative treatment options as small molecule inhibitors aimed at signaling pathway disruptions, immunotherapy, including checkpoint inhibitors, oncolytic vaccines, CAR T-cell therapy, and drug delivery systems. In terms of an innovative approach, the elaboration of targeted drug delivery systems is of particular interest, since this strategy looks the most promising due to its ability to increase the bioavailability and effectiveness of both standard and newly tested agents. This review discusses results of preclinical and clinical studies of innovative therapeutic approaches, their advantages and disadvantages. An interdisciplinary approach is expected to be able to combine the results of cutting-edge research in this area and to provide novel promising therapeutic strategies for patients with GBM.
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