Targeting CDK1 in cancer: mechanisms and implications.
Targeting CDK1 in cancer: mechanisms and implications.
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DOI：
10.1038/s41698-023-00407-7
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发表时间：
2023-06-13
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
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作者：
细胞周期蛋白依赖性蛋白激酶(CDK)是一类丝氨酸/苏氨酸激酶，被认为是肿瘤治疗的候选靶点。这些与细胞周期蛋白络合的蛋白质在细胞周期进程中起着关键作用。根据TCGA数据库，大多数CDK在癌症组织中的表达明显高于正常组织，并与多种癌症类型的存活率相关。CDK1的去调控已被证明与肿瘤的发生密切相关。CDK1的激活在多种癌症类型中起着关键作用，其多种底物的磷酸化极大地影响了它们在肿瘤发生中的作用。利用京都基因和基因组百科全书(KEGG)对CDK1相互作用蛋白进行富集化分析，证实相关蛋白参与多种致癌途径。这些丰富的证据清楚地支持CDK1作为癌症治疗的有希望的靶点。许多针对CDK1或多个CDK的小分子已经被开发出来，并在临床前研究中进行了评估。值得注意的是，其中一些小分子也进行了人体临床试验。本文就靶向CDK1在肿瘤发生和肿瘤治疗中的作用机制和意义作一综述。
Cyclin dependent kinases (CDKs) are serine/threonine kinases that are proposed as promising candidate targets for cancer treatment. These proteins complexed with cyclins play a critical role in cell cycle progression. Most CDKs demonstrate substantially higher expression in cancer tissues compared with normal tissues and, according to the TCGA database, correlate with survival rate in multiple cancer types. Deregulation of CDK1 has been shown to be closely associated with tumorigenesis. CDK1 activation plays a critical role in a wide range of cancer types; and CDK1 phosphorylation of its many substrates greatly influences their function in tumorigenesis. Enrichment of CDK1 interacting proteins with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to demonstrate that the associated proteins participate in multiple oncogenic pathways. This abundance of evidence clearly supports CDK1 as a promising target for cancer therapy. A number of small molecules targeting CDK1 or multiple CDKs have been developed and evaluated in preclinical studies. Notably, some of these small molecules have also been subjected to human clinical trials. This review evaluates the mechanisms and implications of targeting CDK1 in tumorigenesis and cancer therapy.
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影响因子：
14.9
作者：
McKerlie M;Walker JR;Mitchell TR;Wilson FR;Zhu XD
通讯作者：
Zhu XD
影响因子：
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作者：
Boufraqech M;Wei D;Weyemi U;Zhang L;Quezado M;Kalab P;Kebebew E
通讯作者：
Kebebew E
影响因子：
11.1
作者：
Cepeda, Diana;Ng, Hwee-Fang;Sharifi, Hamid Reza;Mahmoudi, Salah;Soto Cerrato, Vanessa;Fredlund, Erik;Magnusson, Kristina;Nilsson, Helen;Malyukova, Alena;Rantala, Juha;Klevebring, Daniel;Vinals, Francesc;Bhaskaran, Nimesh;Zakaria, Siti Mariam;Rahmanto, Aldwin Suryo;Grotegut, Stefan;Nielsen, Michael Lund;Szigyarto, Cristina Al-Khalili;Sun, Dahui;Lerner, Mikael;Navani, Sanjay;Widschwendter, Martin;Uhlen, Mathias;Jirstrom, Karin;Ponten, Fredrik;Wohlschlegel, James;Grander, Dan;Spruck, Charles;Larsson, Lars-Gunnar;Sangfelt, Olle
通讯作者：
Sangfelt, Olle
黄叶替醇在复发多发性骨髓瘤中进行的I期试验。
影响因子：
3
作者：
Hofmeister, Craig C.;Poi, Ming;Bowers, Mindy A.;Zhao, Weiqiang;Phelps, Mitch A.;Benson, Don M.;Kraut, Eric H.;Farag, Sherif;Efebera, Yvonne A.;Sexton, Jennifer;Lin, Thomas S.;Grever, Michael;Byrd, John C.
通讯作者：
Byrd, John C.
影响因子：
8.8
作者：
通讯作者：
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