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举报
2007-03-13 21:04
Title：Notch Signaling, γ-Secretase Inhibitors, and Cancer Therapy
Notch 信号通路，γ-分泌酶抑制剂与癌症治疗 Author: Shih IeM, Wang TL. Resource：Cancer Res. 2007 Mar 1;67(5):1879-82. Impact Factor：8.0（2005） Abstract：The Notch signaling pathway represents a critical component in the molecular circuits that control cell fate during development. Aberrant activation of this pathway contributes to tumorigenesis. The role of Notch in human cancer has been highlighted recently by the presence of activating mutations and amplification of Notch genes in human cancer and by the demonstration that genes in the Notch signaling pathway could be potential therapeutic targets. It has become clear that one of the major therapeutic targets in the Notch pathway are the Notch receptors, in which gamma-secretase inhibitors prevent the generation of the oncogenic (intracellular) domain of Notch molecules and suppress the Notch activity. This review article summarizes the biological roles of Notch molecules in cancer development with special emphasis on the promise and challenges in applying gamma-secretase inhibitors as a new line of targeted therapeutic agents. 在控制细胞发育命运的分子通路中，Notch信号通路是其中一个关键的代表。该通路的异常激活会导致肿瘤发生。Notch在人类肿瘤中的作用最近已经被高度重视，因为在人类肿瘤中出现了Notch基因的活性突变和扩增，而且表明了Notch信号通路上的基因可以成为潜在的癌症治疗靶点。越来越清楚的是，Notch 受体已经成为Notch 通路中一个主要的治疗靶点，γ-分泌酶抑制剂通过该受体能阻止Notch 分子的癌基因结构域（位于细胞内）的形成并且能抑制Notch活性。本综述总结了Notch信号通路分子在肿瘤发生中的生物学作用，同时，特别强调了作为一个新的癌症治疗靶点药物γ-分泌酶抑制剂在应用中的机遇和挑战。 PMID: 17332312 |
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