Development of CDK4/6 Inhibitors: A Five Years Update

The inhibition of cyclin dependent kinases 4 and 6 plays a role in aromatase inhibitor resistant metastatic breast cancer. Three dual CDK4/6 inhibitors have been approved for the breast cancer treatment that, in combination with the endocrine therapy, dramatically improved the survival outcomes both in first and later line settings. The developments of the last five years in the search for new selective CDK4/6 inhibitors with increased selectivity, treatment efficacy, and reduced adverse effects are reviewed, considering the small-molecule inhibitors and proteolysis-targeting chimeras (PROTACs) approaches, mainly pointing at structure-activity relationships, selectivity against different kinases and antiproliferative activity.

Automated summary

Inhibition of cyclin dependent kinases 4 and 6 has shown efficacy in treating aromatase inhibitor resistant metastatic breast cancer. Recent advancements have led to the development of new selective CDK4/6 inhibitors with enhanced selectivity and treatment efficacy, aiming to reduce adverse effects.