Targeting CDKs in the RNAPII transcription cycle.

Targeting transcriptional CDKs offers promising therapeutic potential, with over 15 years of research revealing their critical role in gene regulation and cancer vulnerabilities.

• Why it matters: Dysregulation of transcriptional processes in cancer creates vulnerabilities that can be exploited for therapy, but understanding of how to effectively target these CDKs remains incomplete.
• What they did: The review discusses current knowledge of CDK regulation of all transcription stages, examines dysregulation in cancer, and summarizes advances in therapeutic strategies including inhibitors, degraders, and proximity-inducing modalities.
• The result: These approaches could rewire transcriptional networks in vivo, but addressing mechanistic, translational, and clinical challenges is essential to fully realize their therapeutic potential.