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AKT 作为癌症治疗靶点。

AKT as a Therapeutic Target for Cancer.

机构信息

Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.

China-US (Henan) Hormel Cancer Institute, Jinshui District, Zhengzhou, Henan, China.

出版信息

Cancer Res. 2019 Mar 15;79(6):1019-1031. doi: 10.1158/0008-5472.CAN-18-2738. Epub 2019 Feb 26.

Abstract

Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositide-dependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen synthase kinase 3 beta (GSK3β), or forkhead box protein O1 (FOXO1). The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy. In this review, we discuss the rationale for targeting AKT and also provide details regarding synthetic and natural AKT-targeting compounds and their associated studies.

摘要

许多癌症中的细胞过程归因于激酶信号网络。V-akt 鼠胸腺瘤病毒癌基因同源物 (AKT) 在 PI3K/AKT 信号通路中发挥主要作用。AKT 被 PI3K 或磷酸肌醇依赖性激酶 (PDK) 以及生长因子、炎症和 DNA 损伤激活。信号转导通过下游效应物如 mTOR、糖原合成酶激酶 3β (GSK3β) 或叉头框蛋白 O1 (FOXO1) 发生。AKT 的异常过表达或激活已在许多癌症中观察到,包括卵巢癌、肺癌和胰腺癌,并且与癌细胞增殖和存活增加相关。因此,靶向 AKT 可能为癌症的预防和治疗提供重要方法。在这篇综述中,我们讨论了靶向 AKT 的基本原理,并详细介绍了合成和天然 AKT 靶向化合物及其相关研究。

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