Arrested Developments: CDK4/6 Inhibitor Resistance and Alterations in the Tumor Immune Microenvironment.The uncontrolled proliferation of cancer cells has led to the development of small-molecule inhibitors to target cell-cycle progression.  Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer and testing in other cancer types is underway.  However, resistance to CDK4/6 inhibitors frequently develops.  Here, we review recent studies that provide the preclinical rationale for treatment combinations and schedules that include CDK4/6 inhibitors. 
CDK4/6 Inhibitor
Palbociclib, ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle. 
Palbociclib
Palbociclib, ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle. 
Ribociclib
Palbociclib, ribociclib, and abemaciclib are ATP-competitive inhibitors of cyclin-dependent kinases 4/6 (CDK4/6), which function early within the G1 phase of the cell cycle. 
Abemaciclib
Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer and testing in other cancer types is underway. 
FDA
Recently, CDK4/6 inhibitors have gained FDA approval in postmenopausal estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer and testing in other cancer types is underway.  However, resistance to CDK4/6 inhibitors frequently develops.  Here, we review recent studies that provide the preclinical rationale for treatment combinations and schedules that include CDK4/6 inhibitors. 
CDK4/6 inhibitors