Wei Dai, Dong Xie, Hao Huang, Jingxuan Li, Caiyao Guo, Fuqiang Cao, Luo Yang, Chengyong Zhong, Shenglan Liu. New insights into the dule roles CDK12 in human cancers: mechanisms and interventions for cancer therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101173
Citation:
Wei Dai, Dong Xie, Hao Huang, Jingxuan Li, Caiyao Guo, Fuqiang Cao, Luo Yang, Chengyong Zhong, Shenglan Liu. New insights into the dule roles CDK12 in human cancers: mechanisms and interventions for cancer therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101173
Wei Dai, Dong Xie, Hao Huang, Jingxuan Li, Caiyao Guo, Fuqiang Cao, Luo Yang, Chengyong Zhong, Shenglan Liu. New insights into the dule roles CDK12 in human cancers: mechanisms and interventions for cancer therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101173
Citation:
Wei Dai, Dong Xie, Hao Huang, Jingxuan Li, Caiyao Guo, Fuqiang Cao, Luo Yang, Chengyong Zhong, Shenglan Liu. New insights into the dule roles CDK12 in human cancers: mechanisms and interventions for cancer therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101173
a Jiangxi Provincial Key Laboratory of Pharmacology of Traditional Chinese Medicine, School of Pharmacy, Gannan Medical University, Ganzhou 314000, China;
b Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Jiangxi Provincial Key Laboratory of Tissue Engineering, School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, China;
c Department of Rehabilitation, the Second Affiliated Hospital of Zhejiang University, Hangzhou 310051, China;
d State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510000, China;
e Department of Pathology, First Affiliated Hospital of Gannan Medical University, Ganzhou 314000, China
Funds:
This work was supported by National Natural Science Foundation of China (82260718, 82460716 and 82111530101), Natural Science Foundation of Jiangxi Province, China (20224BAB216121, 20232BAB216137 and 20242BAB25579) and Jiangxi Provincial Thousand Talents Training Program for high level entrepreneurial and innovative talents (jxsq2019201106) and Ganzhou “Taking the Lead” youth project of Technology Innovation Empowerment (JBGS20230001).
The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.
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