Notch 抑制剂在癌症治疗中的应用。
Notch inhibitors for cancer treatment.
机构信息
University of Mississippi, Cancer Institute, Jackson, MS, United States.
出版信息
Pharmacol Ther. 2013 Aug;139(2):95-110. doi: 10.1016/j.pharmthera.2013.02.003. Epub 2013 Feb 28.
Abstract
Notch signaling is an evolutionarily conserved cell signaling pathway involved in cell fate during development, stem cell renewal and differentiation in postnatal tissues. Roles for Notch in carcinogenesis, in the biology of cancer stem cells and tumor angiogenesis have been reported. These features identify Notch as a potential therapeutic target in oncology. Based on the molecular structure of Notch receptor, Notch ligands and Notch activators, a set of Notch pathway inhibitors have been developed. Most of these inhibitors had shown anti-tumor effects in preclinical studies. At the same time, the combinatorial effect of these inhibitors with current chemotherapeutical drugs is still under study in different clinical trials. In this review, we describe the basics of Notch signaling and the role of Notch in normal and cancer stem cells as a logic way to develop different Notch inhibitors and their current stage of progress for cancer patient's treatment.
摘要
Notch 信号通路是一种进化上保守的细胞信号通路，参与发育过程中的细胞命运决定、出生后组织中的干细胞更新和分化。 Notch 在癌症发生、癌症干细胞生物学和肿瘤血管生成中的作用已有报道。这些特征将 Notch 鉴定为肿瘤学中的一个潜在治疗靶点。基于 Notch 受体、Notch 配体和 Notch 激活剂的分子结构，已经开发了一系列 Notch 通路抑制剂。这些抑制剂中的大多数在临床前研究中显示出抗肿瘤作用。同时，这些抑制剂与当前化疗药物的联合作用仍在不同临床试验中进行研究。在这篇综述中，我们描述了 Notch 信号通路的基础知识以及 Notch 在正常和癌症干细胞中的作用，这为开发不同的 Notch 抑制剂及其治疗癌症患者的最新进展提供了逻辑依据。
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