CDK (cyclin-dependent kinase) 4 and CDK6 are key players in cell cycle progression. In many human cancers, CDK6 is overactive, for example one third of medulloblastoma patients show upregulated CDK6. In 2015, FDA has granted an approval to CDK4/6 inhibitor palbociclib (Ibrance) as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. However, per NCCN 2016 guideline for breast cancer, this treatment regime does not require the amplification of CDK4/6. Palbociclib, along with other CDK inhibitors, are actively under many other clinical trials targeting liposarcoma, various advanced solid tumors and hematologic malignancies.