Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253, F-75993 Paris, France; Université Paris Descartes-Sorbonne Paris Cité, F-75012 Paris, France.
Pharmacol Ther. 2018 Apr;184:13-41. doi: 10.1016/j.pharmthera.2017.10.017. Epub 2017 Nov 8.
Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.
尽管神经外科技术和放化疗取得了进展，但脑肿瘤的治疗仍然是一个挑战。对于最常见和致命的成人脑肿瘤胶质母细胞瘤（GB）来说尤其如此。在诊断时，GB 患者的平均存活时间仍仅约为 15 个月。烷化剂替莫唑胺（TMZ）常规用于脑肿瘤患者，诱导细胞凋亡、自噬和未折叠蛋白反应（UPR）。在这里，我们回顾了这些细胞机制及其对脑肿瘤中 TMZ 耐药性的贡献，特别强调了 TMZ 在神经胶质瘤干细胞和 GB 中的耐药性。
