有希望成为肿瘤治疗靶点：细胞核中受体的裂解激活。

IF 6.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2024-09-25 DOI:10.1016/j.drudis.2024.104192

Mengdie Fu, Jin He, Danji Zhu, Qinmeng Zhang, Zhiwei Jiang, Guoli Yang

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引用次数: 0

摘要

总结了细胞表面受体在细胞核内被裂解激活的新命运。细胞表面受体的胞内结构域（ICD）在γ-分泌酶等酶的作用下被裂解，转运到细胞核中形成转录复合物，参与肿瘤的发生和发展。这种命运具有重要的临床意义，因为裂解酶抑制剂通过减少致瘤 ICD，显示出治疗晚期肿瘤的有效性。此外，合成受体的构建也符合命运机制。这篇综述详细介绍了细胞核中裂解激活的每个步骤，阐明了致瘤机制，探讨了在抗肿瘤治疗中的应用，并仔细研究了可能存在的局限性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Promising therapeutic targets for tumor treatment: Cleaved activation of receptors in the nucleus

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Promising therapeutic targets for tumor treatment: Cleaved activation of receptors in the nucleus

A new fate of cell surface receptors, cleaved activation in the nucleus, is summarized. The intracellular domain (ICD) of cell surface receptors, cleaved by enzymes like γ-secretase, translocates to the nucleus to form transcriptional complexes participating in the onset and development of tumors. The fate is clinically significant, as inhibitors of cleavage enzymes have shown effectiveness in treating advanced tumors by reducing tumorigenic ICDs. Additionally, the construction of synthetic receptors also conforms with the fate mechanism. This review details each step of cleaved activation in the nucleus, elucidates tumorigenic mechanisms, explores application in antitumor therapy, and scrutinizes possible limitations.

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来源期刊

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.