Tumour suppressor genes TP53 and RB are frequently mutated or deleted resulting in loss of function in a range of cancer types. Previous work from this laboratory has shown that HPV transformed cervical cancers that are defective for p53 and RB are selectively sensitive to Aurora Kinase B inhibitors (AURKBi). Cells with functional p53 and RB cell cycle arrest and eventually senesce in response to AURKB inhibition, whereas cells defective for these tumour suppressors undergo multiple rounds of endoreplication and failed cytokinesis to become endoreplicating giant polyploid cells. AURKBi treatment of p53 and RB functional cells shows an altered transcriptional profile especially in genes repressed by the DREAM complex and those regulated by E2F and FOXM1. AURKB may be involved directly in the dephosphorylation of RB by disrupting RB and PP1 interaction. AURKBi treatment also leads to the inhibition of CDK2/Cyclin E which is essential for the senescence outcome. I have used high content imaging and a range of cell cycle reporters to investigate how AURKBi promotes senescence in the RB and p53 functional cell lines, and the individual contributions of RB and p53 to the senescence program. Understanding the mechanism through which AURKBi triggers senescence in RB and p53 functional cells, and whether this is loss of RB and/or p53 function, whether any defect in the RB and/or p53 signalling pathways is sufficient to bypass senescence, and the consequences of failing to senesce in the RB/p53 defective cells will help us in designing therapies which are selective for RB and/or p53 defective cancers.