Roles of CDK12/CDK13 and development of inhibitors and degraders

Cancer poses a significant threat to human health and lifespan and remains a persistent focus of biomedical research. Cyclin-dependent kinases 12 and 13 (CDK12/13) serve as crucial regulators of transcript elongation, the DNA damage response (DDR), and the maintenance of genomic stability. The selective inhibition of these kinases is highly effective in cancer therapy. This study systematically reviews the current landscape of the development of CDK12/13 inhibitors and degraders, elucidating their roles in various tumor types, with a particular emphasis on the applications in breast cancer. The advancement of CDK12/13-targeted therapeutics represents a convergence of fields and produces proven clinical benefits in oncology, pharmacology, and related disciplines. Consequently, elucidating the therapeutic mechanisms of CDK12/13 inhibition has significant translational value for precision oncology. In addition, through bioinformatics techniques, we identified new candidate targets for CDK12/13, contributing to the enrichment of the regulatory network of CDK12/13.