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胶质母细胞瘤治疗药物的最新进展。

Current Development of Glioblastoma Therapeutic Agents.

机构信息

Chicago BioSolutions, Inc., Chicago, Illinois.

Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.

出版信息

Mol Cancer Ther. 2021 Sep;20(9):1521-1532. doi: 10.1158/1535-7163.MCT-21-0159. Epub 2021 Jun 25.

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans. Over the past several decades, despite improvements in neurosurgical techniques, development of powerful chemotherapeutic agents, advances in radiotherapy, and comprehensive genomic profiling and molecular characterization, treatment of GBM has achieved very limited success in increasing overall survival. Thus, identifying and understanding the key molecules and barriers responsible for the malignant phenotypes and treatment resistance of GBM will yield new potential therapeutic targets. We review the most recent development of receptor tyrosine kinase targeted therapy for GBM and discuss the current status of several novel strategies with the emphasis on blood-brain barrier penetration as a major obstacle for small-molecule drugs to achieve their therapeutic goals. Likewise, a major opportunity for the treatment of GBM lies in the use of biomarkers for the discovery and development of new receptor tyrosine kinase targeted therapy.

摘要

胶质母细胞瘤(GBM)是人类中最常见和侵袭性最强的恶性原发性脑肿瘤。在过去的几十年中,尽管神经外科技术有所提高,强力化疗药物的开发,放射治疗的进步以及全面的基因组分析和分子特征分析,但在提高总体生存率方面,GBM 的治疗仅取得了非常有限的成功。因此,确定和了解导致 GBM 恶性表型和治疗耐药性的关键分子和障碍将产生新的潜在治疗靶标。我们回顾了用于 GBM 的受体酪氨酸激酶靶向治疗的最新进展,并讨论了几种新型策略的现状,重点是血脑屏障穿透作为小分子药物实现其治疗目标的主要障碍。同样,GBM 治疗的主要机会在于使用生物标志物来发现和开发新的受体酪氨酸激酶靶向治疗。

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