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颅内肿瘤靶向药物治疗的新策略

英文原题:New approaches to targeted drug therapy of intracranial tumors.

PubMed 2025/03/20(内容时间) Cell Death Discov Q1 · IF 10.4(JCR 2025)

研究概要

颅内肿瘤涵盖一组异质性肿瘤,包括胶质瘤、脑膜瘤、垂体腺瘤、神经鞘瘤、颅咽管瘤、室管膜瘤、髓母细胞瘤和原发性中枢神经系统淋巴瘤。

中文摘要

颅内肿瘤包括一组异质性肿瘤,例如胶质瘤、脑膜瘤、垂体腺瘤、神经鞘瘤、颅咽管瘤、室管膜瘤、髓母细胞瘤和原发性中枢神经系统淋巴瘤。由于分子特征多样、位置关键,以及血脑屏障(BBB)和血肿瘤屏障(BTB)构成独特障碍,这些肿瘤治疗具有重大挑战;两种屏障均限制全身治疗的疗效。分子生物学和基因组学的近期进展使特定分子通路和靶点得以识别,为创新精准治疗铺平道路。本综述考察颅内肿瘤靶向治疗的现状,包括受体酪氨酸激酶(RTK)抑制剂、PI3K/AKT/mTOR 抑制剂、RAF/MEK/ERK 通路抑制剂、IDH 突变抑制剂、免疫检查点抑制剂以及 CAR-T 细胞疗法。综述重点讨论 BBB 和 BTB 对药物递送及治疗结局的调节作用,并探讨聚焦超声、纳米颗粒递送系统和对流增强递送等克服屏障的策略。文章还回顾临床试验数据,概述不同肿瘤类型中的成功经验和局限,并介绍新兴治疗方法,包括联合方案以及基于分子分型的个体化治疗。通过综合最新研究,本文旨在全面阐释颅内肿瘤靶向治疗的进展和持续存在的挑战。研究结果强调,需要创新递送系统并开展更大规模临床试验,以优化治疗策略。本综述希望为未来研究和临床实践提供参考,改善这些复杂、危及生命疾病患者的结局与生活质量。

展开英文摘要原文

Intracranial tumors encompass a heterogeneous group of neoplasms, including gliomas, meningiomas, pituitary adenomas, schwannomas, craniopharyngiomas, ependymomas, medulloblastomas, and primary central nervous system lymphomas. These tumors present significant challenges due to their diverse molecular characteristics, critical locations, and the unique obstacles posed by the blood-brain barrier (BBB) and blood-tumor barrier (BTB), which limit the efficacy of systemic therapies. Recent advances in molecular biology and genomics have enabled the identification of specific molecular pathways and targets, paving the way for innovative precision therapies. This review examines the current state of targeted therapies for intracranial tumors, including receptor tyrosine kinase (RTK) inhibitors, PI3K/AKT/mTOR inhibitors, RAF/MEK/ERK pathway inhibitors, IDH mutation inhibitors, immune checkpoint inhibitors, and CAR-T cell therapies. Emphasis is placed on the role of the BBB and BTB in modulating drug delivery and therapeutic outcomes. Strategies to overcome these barriers, such as focused ultrasound, nanoparticle-based delivery systems, and convection-enhanced delivery, are also explored. Furthermore, the manuscript reviews clinical trial data, highlighting successes and limitations across different tumor types. It delves into emerging therapeutic approaches, including combination of regimens and personalized treatments based on molecular profiling. By synthesizing the latest research, this article aims to provide a comprehensive understanding of the advancements and ongoing challenges in the targeted treatment of intracranial tumors. The findings underscore the necessity for innovative delivery systems and more extensive clinical trials to optimize therapeutic strategies. This review aspires to inform future research and clinical practices, aiming to improve patient outcomes and quality of life in the management of these complex and life-threatening conditions.

论文信息

作者
Beylerli O、Gareev I、Musaev E、Roumiantsev S、Chekhonin V、Ahmad A、Chao Y、Yang G
第一作者单位
Central Research Laboratory, Bashkir State Medical University, Ufa, Republic of Bashkortostan, Russian Federation. obeylerli@mail.ru.Russia
通讯作者单位
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. yangguang@hrbmu.edu.cn.China
文献类型
综述
期刊
Cell death discovery2025 Mar 20
原文标识
PubMed 40113789 · DOI 10.1038/s41420-025-02358-3