New approaches to targeted drug therapy of intracranial tumors.

IF 6.1 2区生物学 Q1 CELL BIOLOGY Cell Death Discovery Pub Date : 2025-03-20 DOI:10.1038/s41420-025-02358-3

Ozal Beylerli, Ilgiz Gareev, Elmar Musaev, Sergey Roumiantsev, Vladimir Chekhonin, Aamir Ahmad, Yuan Chao, Guang Yang

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Abstract

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.

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颅内肿瘤靶向药物治疗的新方法。

颅内肿瘤包括胶质瘤、脑膜瘤、垂体腺瘤、分裂瘤、颅咽管瘤、外胚瘤、髓母细胞瘤和原发性中枢神经系统淋巴瘤等多种肿瘤。由于这些肿瘤具有不同的分子特征、关键位置以及血脑屏障（BBB）和血瘤屏障（BTB）所造成的独特障碍，限制了全身疗法的疗效，因此面临着巨大的挑战。分子生物学和基因组学的最新进展使人们能够确定特定的分子通路和靶点，为创新的精准疗法铺平了道路。本综述探讨了颅内肿瘤靶向疗法的现状，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、免疫检查点抑制剂和CAR-T细胞疗法。重点是 BBB 和 BTB 在调节药物输送和治疗效果方面的作用。还探讨了克服这些障碍的策略，如聚焦超声、基于纳米颗粒的给药系统和对流增强给药。此外，手稿还回顾了临床试验数据，强调了不同肿瘤类型的成功经验和局限性。书稿还深入探讨了新出现的治疗方法，包括联合疗法和基于分子图谱的个性化治疗。通过综合最新研究成果，本文旨在让人们全面了解颅内肿瘤靶向治疗的进展和当前面临的挑战。研究结果强调了创新给药系统和更广泛的临床试验对优化治疗策略的必要性。这篇综述旨在为未来的研究和临床实践提供参考，从而在治疗这些复杂且危及生命的疾病时改善患者的预后和生活质量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.