Nature：研究发现胶质母细胞瘤新的治疗靶点

近日，得克萨斯大学西南医学中心研究人员在Nature杂志上发表研究论文揭示了为何最常见的致命的脑肿瘤在成人中会复发，并发现了未来治疗的潜在靶点。

胶质母细胞瘤（GBM），目前被认为是不治之症。尽管初始能接受治疗，但这种癌症类型几乎总是会复发。GBM发病率是一个快速增长的肿瘤类型。

根据国家癌症研究所的数据证实这种恶性脑瘤存活率中位数是大约15个月。

Luis Parada博士说：我们发现了一类增长较慢或保持静止状态的脑肿瘤细胞，这类细胞似乎是接受标准治疗药物Temozolomide后癌症复发的最主要原因。

使用GBM遗传工程小鼠模型，研究人员发现静息的肿瘤细胞具有干细胞样行为，干细胞样肿瘤细胞会一直处于静息状态直到被激活。

Parada博士说：在实体肿瘤组织中癌症干细胞的存在仍然是有争议的，我们正在努力更好地了解这些细胞，目前我们现在正面临着的是技术上的障碍，而不是概念上的困扰。

编译自：Study suggests new treatment target for glioblastoma multiforme

doi:10.1038/nature11287
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A restricted cell population propagates glioblastoma growth after chemotherapy

Jian Chen,Yanjiao Li,Tzong-Shiue Yu,Renée M. McKay,Dennis K. Burns,Steven G. Kernie& Luis F. Parada

Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year¹. This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-ΔTK-GFP transgene subpopulation. Ablation of the GFP⁺ cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.