Function of CDK12 in Tumor Initiation and Progression and Its Clinical Consequences
Authors:
D. Vrábel 1; M. Svoboda 2,3; J. Navrátil 2; J. Kohoutek 1
Authors‘ workplace:
Oddělení chemie a toxikologie, Výzkumný ústav veterinárního lékařství, v. v. i., Brno
1; Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno
2; Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno
3
Published in:
Klin Onkol 2014; 27(5): 340-346
Category:
Reviews
doi:
https://doi.org/10.14735/amko2014340
Overview
Cyclin-dependent kinases (CDKs) participate in many cellular processes and play a crucial role in the regulation of cell cycle and transcription processes. Recently, CDK12 was identified as a key factor orchestrating transcription of genes, such as BRCA1, ATM, ATR, FANCI and FANCD2, which are involved in the DNA-damage response pathway. Importantly, inhibition of function of these genes commonly leads to induction of genomic instability followed by cancer development, but the precise contribution of CDK12 to these processes is to be unveiled. Nevertheless, several mutations affecting function of CDK12 were already identified in a variety of tumors of different origin (ovary, breast, prostate, intestine) making tumors sensitive to cytostatics promoting DNA damage (platin derivatives, alkylating regimens) and inhibitors of DNA repair (PARP inhibitors). Such an effect has been already observed in the model of high grade serous ovarian carcinomas. Thus, CDK12 is becoming a potential therapeutic target of drugs causing synthetic lethality in these cells. Our review summarizes most recent information about CDK12 function in cancer and discusses potential use of CDK12 in clinics.
Key words:
cyclin-dependent kinase 12 – mutation – DNA repair – PARP inhibitor – platin cytostatics
This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health No. NT14599-3, development project of the MZe organization No. MZE-00027162/02:2 and institutional resources for supporting the Research Organization provided by the Czech Ministry of Health to MOÚ in 2014 No. MOÚ, 00209805.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Submitted:
15. 9. 2014
Accepted:
25. 9. 2014
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Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2014 Issue 5
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