Cyclin-dependent kinases (CDK) are key proteins responsible for cell cycle control influencing cell proliferation and differentiation. Dysregulation of these control mechanisms can be found in many types of cancer.
The currently available inhibitors of cyclin-dependent kinases palbociclib, ribociclib, and abemaciclib bind to CDK4 and 6 with different affinities, arresting the cell cycle at the G1 checkpoint, preventing the continuation to the cell cycle S phase. The most common adverse effects of these agents include haematological toxicity, nausea, fatigue, and diarrhoea.
Because the inhibition is reversible, the toxicities usually quickly improve after the discontinuation or dose reduction of the agent. CDK4/6 inhibitors are used in the treatment of metastatic, hormone receptor-positive, HER2- -negative breast cancer in combination with endocrine therapies