杜克大学医学中心的研究人员指出，在致命的脑癌中，干细胞对放疗更具抑制效果。而在实验室中，通过对这些癌症干细胞使用一种药物阻断一个特殊的信号通路，并结合放射治疗，研究人员发现这能够杀死更多的神经胶质瘤细胞。
这项研究是在早期研究的基础上进行的。之前的研究表明癌症干细胞抑制放疗的效果比其他癌细胞更强。
杜克大学的研究人员识别了一种信号通路，该通路叫Notch，其是抑制效果增强的潜在原因。Notch同样在正常的干细胞中存在，对细胞之间的交流很重要。这项研究结果发布在11月份后期的的Stem Cells上。
这是研究人员第一次在放疗失败的肿瘤组织中发现Notch通道。这项研究的负责人Jialiang Wang博士介绍说，Notch通路可以作为一个有前途的药物靶标，开发出正确的药物或能阻止真正的有害“家伙”-神经胶质瘤干细胞。
癌症中的干细胞是癌细胞增殖的来源。数百个的癌症干细胞能够快速变成百万的肿瘤细胞。
研究人员使用了一种叫γ-分泌酶抑制剂的药物，该药物能靶向定位Notch通路中一种关键的酶。
这些抑制剂能够对抗肿瘤中异常激活的Notch通路，比如白血病，乳腺癌和脑瘤。在这项研究中，该抑制剂单独使用只是适度的降低了肿瘤细胞的生长，但是在结合了临床的放射疗法后，会引起肿瘤组织中大量的细胞死亡，并显著降低了神经胶质瘤干细胞的生存。因此联合疗法大大增强了对肿瘤细胞生长的抑制。（生物谷Bioon.com）
生物谷推荐原始出处：
STEM CELLS 17 Nov 2009
Notch Promotes Radioresistance of Glioma Stem Cells
Jialiang Wang 1 2 *, Timothy P. Wakeman 3, Justin D. Lathia 4, Anita B. Hjelmeland 4, Xiao-Fan Wang 3, Rebekah R. White 1 2, Jeremy N. Rich 4 *§, Bruce A. Sullenger 1 2 *
1Department of Surgery, Duke University Medical Center, Durham, NC 27710
2Duke Translational Research Institute, Duke University Medical Center, Durham, NC 27710
3Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
4Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195
Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhanced radiation-induced cell death and impaired clonogenic survival of glioma stem cells, but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protected glioma stem cells against radiation. Notch inhibition with GSIs did not alter the DNA damage response of glioma stem cells following radiation, but rather reduced Akt activity and Mcl-1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impaired xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment.
