A guide to transcriptional cyclin-dependent kinases in cancer

Transcriptional cyclin-dependent kinases (tCDKs) are master regulators of gene expression, controlling RNAPII activity and RNA synthesis across multiple phases of the transcription cycle. While highly controlled transcription is essential for all cellular processes and functions, aberrant gene expression or corrupted activities of tCDKs are drivers of oncogenic phenotypes and represent targetable dependencies across a spectrum of human cancers. This has spurred development and evaluation of tCDK inhibitors and degraders in pre-clinical cancer models and clinical trials, with notable successes recently reported. This review will provide a comprehensive account of how different tCDKs control RNAPII transcription, outline how their function and/or expression is dysregulated in cancer, and discuss the therapeutic strategies and tools that have been developed to exploit their tumorigenic contributions.