Our goals are to evaluate the effectiveness of abemaciclib for treating EBV-associated lymphomas. This application builds on our previous study “The CDK4/6 inhibitor abemaciclib (LY2835219) for the treatment of EBV associated lymphomas” approved by Lilly 2015-18. In this study, we focused on EBV-encoded latent membrane protein 2A (LMP2A) and found abemaciclib was effective for treating LMP2A-driven Burkitt lymphoma (BL) in our model. In our new proposal, we will extend our studies to investigate if abemaciclib is effective for treating LMP1-driven BL. LMP1 is also an EBV oncogenic latent membrane protein and a functional homologue of host CD40 receptor. Our data show that LMP1 accelerates tumor onset in λ-MYC BL model and inhibits cell cycle by degrading cyclindependent kinase (CDK) inhibitor p27kip1 indicating that CDK4/6-inhibition of cell cycle progression can be utilized to block EBV LMP1-driven lymphoma development. Overall, we hope to develop new therapies for EBV related cancers.
|Effective start/end date||3/10/20 → 3/9/22|
- Eli Lilly and Company (Agmt 3/10/20)