电离辐射(ionizing radiation，IR)是指能引起被作用物质电离的辐射，这是一种目前治疗胶质母细胞瘤（glioblastoma）最有效的方法，但是这种放射性疗法(radiotherapy)由于存在抗放射性(radioresistance)，因此治疗效果不理想，其中的机制至今尚不清楚。来自杜克大学医学中心(Duke University Medical Center)神经生物学系，外科系，Preston Robert Tisch 脑肿瘤中心（Preston Robert Tisch Brain Tumor Center）等处的研究人员发现癌症干细胞在这一过程中扮演的重要角色：通过DNA损伤检控点(DNA damage checkpoint)应答激活和DNA修复能力的提升赋予胶质瘤细胞抗放射性。这也许说明了以癌症干细胞DNA损伤检验点为靶标的治疗是克服肿瘤抗放射能力，治疗癌症的新希望，也为脑瘤等具有抗放射性的癌症的治疗提供了新思路。这一研究成果公布在12月7日《Nature》杂志上。
这一研究报告的第一作者是杜克大学外科系的鲍仕登(Shideng Bao，音译)博士，早年毕业于武汉大学生科院，于厦门大学获得博士学位。
胶母细胞瘤，即多形性胶质母细胞瘤，世界卫生组织命名为4型神经胶质瘤。这种肿瘤生长快，病程短，是一种最常见的脑胶质瘤之一，占胶质瘤的25%以上，也是最恶性的一种。目前主要的治疗的方法就是手术切除与术后放疗等结合，但是由于胶质母细胞瘤对放射性等治疗方法有高度抗性并且是致死率极高的脑部肿瘤，所以尽管入侵性治疗能够杀死大多数癌细胞，但是无法作到全部切除，常常重新发展为体积更大的癌细胞团。
这其中到底是什么导致这些肿瘤具有不同寻常的抗性呢？在这篇研究报告中，Bao等人通过动物和培养细胞实验发现在接受放射性治疗后，细胞中DNA损伤检验点应答过程能帮助癌症干细胞开启自发修复DNA损伤的信号，躲过放射波的袭击。
英文原文：
Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.
Ionizing radiation represents the most effective therapy for glioblastoma (World Health Organization grade IV glioma), one of the most lethal human malignancies, but radiotherapy remains only palliative because of radioresistance. The mechanisms underlying tumour radioresistance have remained elusive. Here we show that cancer stem cells contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. The fraction of tumour cells expressing CD133 (Prominin-1), a marker for both neural stem cells and brain cancer stem cells, is enriched after radiation in gliomas. In both cell culture and the brains of immunocompromised mice, CD133-expressing glioma cells survive ionizing radiation in increased proportions relative to most tumour cells, which lack CD133. CD133-expressing tumour cells isolated from both human glioma xenografts and primary patient glioblastoma specimens preferentially activate the DNA damage checkpoint in response to radiation, and repair radiation-induced DNA damage more effectively than CD133-negative tumour cells. In addition, the radioresistance of CD133-positive glioma stem cells can be reversed with a specific inhibitor of the Chk1 and Chk2 checkpoint kinases. Our results suggest that CD133-positive tumour cells represent the cellular population that confers glioma radioresistance and could be the source of tumour recurrence after radiation. Targeting DNA damage checkpoint response in cancer stem cells may overcome this radioresistance and provide a therapeutic model for malignant brain cancers.
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