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.

中文翻译：

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胶质母细胞瘤治疗药物的当前发展

多形性胶质母细胞瘤 (GBM) 是人类最常见和最具侵袭性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改进，强大的化学治疗剂的开发，放射疗法的进步以及全面的基因组分析和分子表征，但 GBM 的治疗在提高总体生存率方面取得的成功非常有限。因此，识别和了解导致 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点。我们回顾了针对 GBM 的受体酪氨酸激酶靶向治疗的最新进展，并讨论了几种新策略的现状，重点是血脑屏障穿透是小分子药物实现其治疗目标的主要障碍。同样，治疗 GBM 的一个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。