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Therapeutic potential of targeting polo-like kinase 4

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机构： [1]Department of Respiratory and Critical Care Medicine, West China Hospital and Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. [2]Laboratory of Clinical Pharmacy and Adverse Drug Reaction, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. [3]Department of Pharmacy, Guizhou Provincial People's Hospital, Guizhou, Guiyang, 550002, China. [4]Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. [5]Department of Emergency Medicine and Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

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关键词： Polo-like kinase 4 (PLK4) Centrosome duplication PLK4 inhibitors Cancer therapy Drug discovery

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Polo-like kinase 4 (PLK4), a highly conserved serine/threonine kinase, masterfully regulates centriole duplication in a spatiotemporal manner to ensure the fidelity of centrosome duplication and proper mitosis. Abnormal expression of PLK4 contributes to genomic instability and associates with a poor prognosis in cancer. Inhibition of PLK4 is demonstrated to exhibit significant efficacy against various types of human cancers, further highlighting its potential as a promising therapeutic target for cancer treatment. As such, numerous small-molecule inhibitors with distinct chemical scaffolds targeting PLK4 have been extensively investigated for the treatment of different human cancers, with several undergoing clinical evaluation (e.g., CFI-400945). Here, we review the structure, distribution, and biological functions of PLK4, encapsulate its intricate regulatory mechanisms of expression, and highlighting its multifaceted roles in cancer development and metastasis. Moreover, the recent advancements of PLK4 inhibitors in patent or literature are summarized, and their therapeutic potential as monotherapies or combination therapies with other anticancer agents are also discussed.Copyright © 2024 Elsevier Masson SAS. All rights reserved.

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大类 | 2 区

医学

小类 | 1 区药物化学

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第一作者机构： [1]Department of Respiratory and Critical Care Medicine, West China Hospital and Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

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