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肿瘤学中靶向CDK7:前进的道路。

Targeting CDK7 in oncology: The avenue forward.

作者信息

Li Zhi-Mei, Liu Guan, Gao Ya, Zhao Ming-Gao

机构信息

Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, PR China.

Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xinsi Road 1, Xi'an 710038, Shaanxi, PR China.

出版信息

Pharmacol Ther. 2022 Dec;240:108229. doi: 10.1016/j.pharmthera.2022.108229. Epub 2022 Jun 11.

Abstract

Cyclin-dependent kinase (CDK) 7 is best characterized for the ability to regulate biological processes, including the cell cycle and gene transcription. Abnormal CDK7 activity is observed in various tumours and represents a driving force for tumourigenesis. Therefore, CDK7 may be an appealing target for cancer treatment. Whereas, the enthusiasm for CDK7-targeted therapeutic strategy is mitigated due to the widely possessed belief that this protein is essential for normal cells. Indeed, the fact confronts the consensus. This is the first review to introduce the role of CDK7 in pan-cancers via a combined analysis of comprehensive gene information and (pre)clinical research results. We also discuss the recent advances in protein structure and summarize the understanding of mechanisms underlying CDK7 function. These endeavours highlight the pivotal roles of CDK7 in tumours and may contribute to the development of effective CDK7 inhibitors within the strategy of structure-based drug discovery for cancer therapy.

摘要

细胞周期蛋白依赖性激酶(CDK)7最显著的特点是能够调节包括细胞周期和基因转录在内的生物学过程。在各种肿瘤中均观察到CDK7活性异常,这是肿瘤发生的驱动力。因此,CDK7可能是一个有吸引力的癌症治疗靶点。然而,由于人们普遍认为这种蛋白质对正常细胞至关重要,针对CDK7的治疗策略的热情有所降低。事实上,事实与这种共识相悖。这是第一篇通过综合基因信息和(临床前)临床研究结果的联合分析来介绍CDK7在泛癌中的作用的综述。我们还讨论了蛋白质结构的最新进展,并总结了对CDK7功能潜在机制的理解。这些努力突出了CDK7在肿瘤中的关键作用,并可能有助于在基于结构的癌症治疗药物发现策略中开发有效的CDK7抑制剂。

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