CDK (cyclin-dependent kinase) 4 and CDK6 are key players in cell cycle progression. In many human cancers, CDK4 is overactive, such as liposarcoma. 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 clinical trials targeting liposarcoma, various advanced solid tumors and hematologic malignancies.