Dr. Xi (Hill) Liu

Frederick National Laboratory for Cancer Research
Molecular Pharmacology Program

Friday, October 15, 2021
12:00 Noon
Host: Dr. Chengpeng Chen

“Engaging Anaphase Catastrophe to Eradicate Aneuploid Cancers”

Our team seeks to reverse deregulated cancer cell growth by exploiting genomic instability (aneuploidy). We identified a mechanism that we designated as anaphase catastrophe that targets aneuploid cancer cells for death by inhibiting cyclin-dependent kinase 2 (Cdk2) activity. CDK2 inhibitor, CYC065, can cause anaphase catastrophe and repress lung cancer growth and metastasis.  To find collaborating agent for CDK2 inhibition, we found that polo-like kinase 4 (PLK4) inhibition can promote centrosome reduplication and mitotic catastrophe.  Combination of CDK2 inhibition and PLK4 inhibition is undergoing.  To better understand the mechanism, we use live-cell imaging and fucci4 probes to study the cell fate under CDK2 inhibition.  Taken together, our investigations are helping to uncover new and potentially cooperative cancer pharmacologic approaches that target a hallmark of cancer, aneuploidy.