The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

// Jeffrey Small 1 , Erik Washburn 2 , Karmaine Millington 2 , Junjia Zhu 3 and Sheldon L. Holder 1 1 Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, PA, USA 2 Department of Pathology and Laboratory Medicine, Penn State Hershey Medical Center, Hershey, PA, USA 3 Department of Public Health Sciences, Penn State University College of Medicine, Hershey, PA, USA Correspondence to: Sheldon L. Holder, email: sholder@pennstatehealth.psu.edu Keywords: PIM1 kinase; CDK4/6 kinase; abemaciclib; renal cell carcinoma; sunitinib Received: November 11, 2016 Accepted: June 29, 2017 Published: July 27, 2017 ABSTRACT Multiple therapies currently exist for renal cell carcinoma, however, most do not result in cure and the development of acquired resistance is the rule rather than the exception. CDK4/6 and PIM1 kinases are potential new therapeutic targets in RCC. Abemaciclib is a potent CDK4/6 and PIM1 kinase inhibitor, thus we evaluated the effects of abemaciclib on renal cell carcinoma. In vitro , abemaciclib causes decreased cellular viability, increased apoptosis, and alterations in autophagy in renal cell carcinoma cell lines. A pre-clinical mouse model of RCC shows abemaciclib in combination with sunitinib to cause dramatic reduction in tumor sizes without overt toxicity. Thus abemaciclib is active in renal cell carcinoma and should be evaluated in a clinical trial in combination with sunitinib. Additionally, CDK4/6 and PIM1 kinase appear to be viable clinical targets in renal cell carcinoma.