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雷帕霉素作用机制靶点抑制剂:作为癌症治疗药物的成功与挑战

Mechanistic target of rapamycin inhibitors: successes and challenges as cancer therapeutics.

作者信息

Bhaoighill Muireann Ní, Dunlop Elaine A

机构信息

Division of Cancer and Genetics, Cardiff University, Cardiff, CF14 4XN, UK.

出版信息

Cancer Drug Resist. 2019 Dec 19;2(4):1069-1085. doi: 10.20517/cdr.2019.87. eCollection 2019.

Abstract

Delineating the contributions of specific cell signalling cascades to the development and maintenance of tumours has greatly informed our understanding of tumorigenesis and has advanced the modern era of targeted cancer therapy. It has been revealed that one of the key pathways regulating cell growth, the phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/mTOR) signalling axis, is commonly dysregulated in cancer. With a specific, well-tolerated inhibitor of mTOR available, the impact of inhibiting this pathway at the level of mTOR has been tested clinically. This review highlights some of the promising results seen with mTOR inhibitors in the clinic and assesses some of the challenges that remain in predicting patient outcome following mTOR-targeted therapy.

摘要

明确特定细胞信号级联反应对肿瘤发生和维持的作用,极大地增进了我们对肿瘤发生的理解,并推动了靶向癌症治疗的现代时代发展。据揭示,调节细胞生长的关键途径之一,即磷脂酰肌醇3激酶/雷帕霉素作用机制靶点(PI3K/mTOR)信号轴,在癌症中通常失调。有了一种特异性、耐受性良好的mTOR抑制剂,在临床上已测试了在mTOR水平抑制该途径的影响。本综述重点介绍了临床上mTOR抑制剂取得的一些有前景的结果,并评估了在预测mTOR靶向治疗后患者预后方面仍然存在的一些挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c8e/9019212/4c91e290f77c/cdr-2-1069.fig.1.jpg

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