Th e role of CDK12 in tumor bio logy

Abstract

Background: Physiological function of cyclin-dependent kinase 12 (CDK12) is crucial for several cellular processes, including regulation of transcription, RNA splicing, transcription termination and polyadenylation. It is well documented by now that CDK12 controls transcription of the unique set of genes involved in DNA-damage response, replication of DNA and response to cellular stress. Just recently, a key function of CDK12 in the induction of tandem duplication of specific DNA sequences within the metastatic castrate resistant prostate tumors has been documented. Therefore, it is possible to recognize CDK12 as a tumor suppressor; nevertheless, there is a growing body of evidence that CDK12 can support tumor growth under specific circumstances and thus act as a tumor oncogene. CDK12 therefore represents an alternative dia-gnostic approach for breast, ovarian and prostate tumors, especially when conventional treatment is not active and there is a need for more effective approaches, such as concept of synthetic lethality.

Methods: The discussed scientific papers can be reached at the PubMed and Scopus databases before 1th of April 2020.

Purpose: The aim of the review is to summarize current knowledge relevant to the function of CDK12 as a tumor suppressor or oncogene in various tumors and to discuss the use of specific CDK12 inhibitors for patient treatment. At the end of the article, we discuss the potential use of CDK12 in the treatment of specific tumors by its targeted inhibition in monotherapy or in combination with poly (ADP ribose) polymerase 1 (PARP1) and checkpoint kinase 1 (CHK1) inhibitors. 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 recommendation for biomedical papers.

Keywords: CDK12; CHK1; PARP1; breast cancer; cyclin-dependent kinase 12; ovarian cancer.