Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues

Abstract

Essential transcription and cell cycle progression controllers are CDKs, whose dysregulation is a defining trait of many human cancers. CDKs have grown to be very crucial therapeutic targets in cancer. Although traditional CDK inhibitors have demonstrated therapeutic efficacy, they frequently encounter limitations due to resistance mechanisms and off-target effects. Recent developments in targeted protein degradation, like proteolysis-targeting chimeras (PROTACs) and molecular glues, offer creative ways to destroy CDK proteins specifically. These techniques reduce scaffolding activities and slow down kinase activity, hence more completely blocking oncogenic CDK signaling. This paper highlights the clinical and preclinical developments of PROTACs and molecular glues, investigates the current CDK-targeting therapeutic landscape, and studies the molecular basis of CDK dysregulation in cancer. We also address their benefits over conventional inhibitors, current issues, and possibilities for inclusion into precision oncology. These new approaches taken together represent a change in CDK-targeted cancer therapy.