Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases that regulate transcriptional and post-transcriptional processes, thereby modulating multiple cellular functions. Early studies characterised CDK12 as a transcriptional CDK that complexes with cyclin K to mediate gene transcription by phosphorylating RNA polymerase II. CDK12 has been demonstrated to specifically upregulate the expression of genes involved in response to DNA damage, stress and heat shock. More recent studies have implicated CDK12 in regulating mRNA splicing, 3’ end processing, pre-replication complex assembly and genomic stability during embryonic development. Genomic alterations in CDK12 have been detected in oesophageal, stomach, breast, endometrial, uterine, ovarian, bladder, colorectal and pancreatic cancers, ranging from 5% to 15% of sequenced cases. An increasing number of studies point to CDK12 inhibition as an effective strategy to inhibit tumour growth, and synthetic lethal interactions have been described with MYC, EWS/FLI and PARP/CHK1 inhibition. Herein, we discuss the present literature on CDK12 in cell function and human cancer, highlighting important roles for CDK12 as a clinical biomarker for treatment response and potential as an effective therapeutic target.
- cancer genetics
- cell biology
- C-MYC oncogene
- breast cancer
- ovarian cancer
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Handling editor Des Richardson.
Contributors GYLL wrote the manuscript and prepared all figures. CG and CJK contributed to writing of the manuscript.
Funding GYLL is funded by the Ovarian Cancer Research Fund Alliance. CJK is funded by grants from the NIH/NCI (U01 CA217883, U54 CA132381).
Competing interests CG and CJK are cofounders of and have ownership interests in SEngine Precision Medicine. GYLL has no competing interests to declare.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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