CDK8 kinase—An emerging target in targeted cancer therapy

•Impeded mRNA synthesis contributes to the effectiveness of pan-CDK inhibitors.•Numerous studies indicate that CDK8/cyclin C can function as a bona fide oncogene.•Oncogenic functions of CDK8 are related to the modulation of transcription programs.•Unique structure of CDK8/CycC among other CDKs enables SBDD of selective inhibitors.•First selective CDK8/cyclin C inhibitors are currently in preclinical development.

Cyclin-dependent kinase (CDK) inhibitors have been developed as potential anticancer therapeutics and several nonselective compounds are currently in advanced clinical trials. This review is focused on the key biological roles of CDK8 kinase, which provide a proof-of-principle for continued efforts toward effective cancer treatment, targeting activity of this CDK family member. Among currently identified kinase inhibitors, several displayed significant selectivity for CDK8 and notably the effectiveness in targeting cancer specific gene expression programs. Structural features of CDK8 and available ligands were discussed from a perspective of the rational drug design process. Current state of the art confirms that further development of CDK8 inhibitors will translate into targeted therapies in oncology. This article is part of a Special Issue entitled:Inhibitors of Protein Kinases.