PURPOSE OF REVIEW: In this article, we not only review the preclinical and 
clinical studies of cyclin-dependent kinase (CDK) 4/6 inhibitors in breast 
cancer, liposarcoma, mantel cell lymphoma, melanoma and germ cell tumors, but 
also examine promising preclinical data in glioblastoma, renal and ovarian 
cancer models that may provide directions for future development.
RECENT FINDINGS: Targeting CDKs has been the focus of considerable basic science 
and clinical research. The CDK 4/6 inhibitors are a novel class of therapeutics 
that target the CDK 4/6 kinases that promote transition through the cell cycle. 
Currently, palbociclib (PD0332991, Pfizer), abemaciclib (LY2835219, Lilly) and 
ribociclib (LEE011, Novartis) are being investigated in clinical trials. These 
oral agents offer the hope of clinical efficacy in many tumor types, and have 
been associated with minimal toxicity. Amplification/overexpression of cyclin D, 
loss of CDKN2A (p16) and amplification/overexpression of CDK4 are proposed 
biomarkers of improved response to CDK4/6 inhibition.
SUMMARY: Palbociclib, abemaciclib and ribociclib have demonstrated very 
promising clinical activity in breast cancer, liposarcoma, mantel cell lymphoma 
and melanoma. Moreover, CDK4/6 inhibitors have shown promising preclinical 
activity in glioblastoma, renal and ovarian cancer models that may provide 
directions for their future clinical development. Further preclinical and 
clinical research is needed to better understand mechanisms of resistance and 
develop rational combination therapies with other targeted agents.