title: [Function of CDK12 in Tumor initiation and progression and its clinical consequences].
abstract: 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.
authors.forename: D
authors.initials: D
authors.lastname: Vrábel
authors.forename: M
authors.initials: M
authors.lastname: Svoboda
authors.forename: J
authors.initials: J
authors.lastname: Navrátil
authors.forename: J
authors.initials: J
authors.lastname: Kohoutek
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D063646:Carcinogenesis / Q000235:genetics; D043171:Chromosomal Instability; D002945:Cisplatin / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C447339:CDK12 protein, human; D018844:Cyclin-Dependent Kinases; D002945:Cisplatin