Department of Radiation Oncology, Tianjin Hospital, Tianjin, 300211, China; Tianjin Medical University, Tianjin, 300070, China.
Frontier Science Center for Synthetic Biology, Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, PR China.
Cancer Lett. 2020 Apr 10;475:79-91. doi: 10.1016/j.canlet.2020.01.027. Epub 2020 Jan 28.
Glioblastoma (GBM) is the most common malignancy of the central nervous system, and most patients with GBM die of the disease despite standard treatment. By clarifying the molecular abnormalities that drive the malignant phenotype of GBM, various drugs that specifically target tumor cells and the tumor microenvironment have been developed. These drugs, including drugs targeting growth factor receptors and their downstream signaling pathways, angiogenesis, aberrant metabolism, epigenetic deregulation, and aberrant immune microenvironments, have been investigated in preclinical or clinical trials. However, these drugs that significantly inhibited the growth of GBM in the preclinical stage have not produced survival benefits in patients with GBM. One reason for their failure is the lack of a definite driver gene to select patients most likely to benefit. Another reason is the inadequate pharmacokinetic properties of the drugs owing of the blood-brain barrier. In the present review, we discuss progress in the development of target therapeutic strategies. Furthermore, we discuss the development of nanomaterials that act as local drug delivery systems to penetrate the blood-brain barrier for managing GBM.
胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤，尽管采用了标准治疗，但大多数 GBM 患者仍死于该疾病。通过阐明驱动 GBM 恶性表型的分子异常，已经开发出了各种专门针对肿瘤细胞和肿瘤微环境的药物。这些药物包括针对生长因子受体及其下游信号通路、血管生成、异常代谢、表观遗传失调和异常免疫微环境的药物，已经在临床前或临床试验中进行了研究。然而，这些在临床前阶段显著抑制 GBM 生长的药物并没有给 GBM 患者带来生存获益。它们失败的一个原因是缺乏明确的驱动基因来选择最有可能受益的患者。另一个原因是由于血脑屏障的存在，药物的药代动力学特性不足。在本综述中，我们讨论了靶向治疗策略的发展进展。此外，我们还讨论了作为局部药物递送系统的纳米材料的发展，以穿透血脑屏障来治疗 GBM。
