Background: Polo-like kinase 4 (PKL4) plays a key role in centriole replication. Hence PLK4 inhibition disrupts mitosis, and offers a novel approach to treating chromosomally unstable cancers, including pancreatic cancer. CFI-400945 is a first in class small molecule PLK4 inhibitor, currently undergoing early phase clinical trials. Results: Treatment with CFI-400945 significantly reduced tumor growth and increased survival in four out of the six models tested. Consistent with PLK4 inhibition, we observed reduced expression of the proliferation marker Ki-67 associated with an increase in nuclear diameter during treatment with CFI-400945. Additionally, treatment with CFI-400945 resulted in a significant reduction of tumor-initiating cells. Discussion: These results support the further investigation of PLK4 as a drug target in pancreatic cancer. Methods: Sensitivity to CFI-400945 was tested in a series of six patientderived pancreatic cancer xenografts, selected to represent the range of growth characteristics, genetic features, and hypoxia found in pancreatic cancer patients.
- Pancreatic cancer
- Patient-derived pancreatic cancer xenografts
- Polo-like kinase 4
ASJC Scopus subject areas