Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors

Abstract Cyclin-dependent kinase (CDK) 4/6 inhibitors have reshaped the therapeutic landscape for hormone receptor (HR)-positive breast cancer and firmly established cell-cycle regulation as a viable target in oncology. Yet, despite strong biological rationale, their clinical impact outside this setting has expanded more slowly than anticipated. This review dissects key gaps in our understanding of CDK4/6–cyclin D signalling and its context-dependent roles in tumourigenesis. We begin by the outlining molecular biology of CDK4, CDK6, and D-type cyclins, highlighting their contributions to