摘要

Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and cross-talk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Because the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway.

译文

自从在黑腹果蝇中首次观察到凹翼表型以来,已经过去了 100 多年,并且在表征凹口受体、其配体、下游靶标的作用方面取得了重大进展, 以及与其他信号通路的串话。具有四个 Notch 受体 (Notch1-4) 和五个配体 (dll1,3-4,Jagged 1-2) 的典型 Notch 通路是一种进化上保守的细胞信号通路,在细胞命运决定、分化、发育、组织模式、细胞增殖和死亡中起关键作用。在癌症中,这些角色对肿瘤行为和治疗反应有关键影响。因为 Notch 的作用仍然是组织和环境依赖性的,该途径内的改变可能导致肿瘤抑制或致癌表型。虽然目前没有 FDA 批准的 Notch 通路治疗方法,但多种治疗方法 (e. g., demcizumab 、 tarixtumab 、 GSI MK-0752 、 R04929097 和 PF63084014) 已被开发用于针对血液系统和实体恶性肿瘤的该途径的不同方面。了解 Notch 通路的上下文特异性效应对于针对该通路的个体化治疗非常重要。

Notch signaling pathway

内分泌 信号通路 临床研究术语
概述  :  

Notch信号通路是存在于大多数动物系统的一种高度保守的细胞信号。哺乳动物拥有四个不同的缺口受体,分别称为NOTCH1,NOTCH2,NOTCH3和NOTCH4。Notch受体是单程跨膜受体蛋白。它是由大的细胞外部分组成的杂合寡聚物,与钙依赖性非共价缔合与由较小的细胞外区域,单个跨膜通道和较小的细胞内区域组成的较小的缺口蛋白相互作用。Notch信号在神经发生过程中促进增殖信号,而Numb抑制其活性以促进神经分化,它在调节胚胎发育中起主要作用。 作

notch   英 /nɒtʃ/   美 /nɑːtʃ/

释    义   n. 刻痕,凹口;等级;峡谷

               vt. 赢得;用刻痕计算;在…上刻凹痕

同根词   notched adj. 有凹口的;有缺口的;有锯齿状的

例    句   It was time to step it up a notch and get my body in shape it deserves.是时候让我的身材更上一层楼了。

 

signaling   英 /'sɪɡnəlɪŋ/

释    义   n. 发信号;打信号

同根词   signal adj. 显著的;作为信号的

               sign n. 迹象;符号;记号;手势

               signed v. 署名;写下;预示;示意(sign的过去分词)

               sign vi. 签署;签名

               sign vt. 签署;示意

例    句   This and our other findings indicate that estrogen directly affects the brain, perhaps by interfering with brain signaling molecules.这和我们其他的观察都暗示了雌激素会直接影响大脑,也许它会妨碍大脑的信号分子。

 

pathway   英 /ˈpɑːθweɪ/   美 /ˈpæθweɪ/

释    义   n. 路,道;途径,路径;神经通路

例    句   You therefore have to find out which pathway is crucial in a cancer before you can make the drug.因此,医生须在制造药物之前找出在某一癌症中起关键作用的分子途径。

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