Úloha CDK12 v iniciaci a rozvoji nádorů a její klinické konsekvence
[Function of CDK12 in Tumor initiation and progression and its clinical consequences]
Language Czech Country Czech Republic Media print
Document type English Abstract, Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
25312711
DOI
10.14735/amko2014340
PII: 49870
- MeSH
- Antineoplastic Agents, Alkylating therapeutic use MeSH
- Chromosomal Instability MeSH
- Cisplatin therapeutic use MeSH
- Cyclin-Dependent Kinases genetics physiology MeSH
- Transcription, Genetic * MeSH
- Carcinogenesis * genetics MeSH
- Humans MeSH
- Mutation MeSH
- Ovarian Neoplasms drug therapy MeSH
- Neoplasms drug therapy genetics MeSH
- DNA Repair * MeSH
- DNA Damage * MeSH
- Antineoplastic Agents therapeutic use MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- English Abstract MeSH
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Antineoplastic Agents, Alkylating MeSH
- CDK12 protein, human MeSH Browser
- Cisplatin MeSH
- Cyclin-Dependent Kinases MeSH
- Antineoplastic Agents MeSH
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 promot-ing 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.
References provided by Crossref.org