Hambardzumyan Dolores, Becher Oren J, Holland Eric C
Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Cell Cycle. 2008 May 15;7(10):1371-8. doi: 10.4161/cc.7.10.5954. Epub 2008 Mar 19.
Gliomas and medulloblastomas are the most frequent malignant brain tumors in adult and children respectively. Although both tumors arise in the CNS, there is a significant difference in their therapeutic response. Medulloblastomas are relatively curable, while glioblastomas are basically incurable. During the last decade several reports have demonstrated the existence of cancer stem cells in brain tumors, their location and their response to treatment. We have recently described the therapeutic response of medulloblastomas to radiation in their native microenvironment, illustrating how p53 and Pi3K signaling pathways lead to the evasion of cell death by the nestin-expressing cells in the perivascular stem cell niche, even while the bulk of tumor succumbs to apoptosis.(1) It remains to be determined whether this mechanism of tumor resistance applies to the more complex stem-cell niche and tumor bulk of gliomas.
胶质瘤和髓母细胞瘤分别是成人和儿童中最常见的恶性脑肿瘤。尽管这两种肿瘤均起源于中枢神经系统,但它们的治疗反应存在显著差异。髓母细胞瘤相对可治愈,而胶质母细胞瘤基本上无法治愈。在过去十年中,有几份报告证明了脑肿瘤中癌症干细胞的存在、其位置及其对治疗的反应。我们最近描述了髓母细胞瘤在其天然微环境中对辐射的治疗反应,阐明了p53和Pi3K信号通路如何导致血管周围干细胞龛中表达巢蛋白的细胞逃避细胞死亡,即使大部分肿瘤细胞发生凋亡。(1) 这种肿瘤耐药机制是否适用于更复杂的胶质瘤干细胞龛和肿瘤主体仍有待确定。