Funding outcome

Cancers are characterized by uncontrolled cell divisions. Cell cycle checkpoints are ways that normal cells control cell division. Cervical cancers are defective in part of the cell cycle checkpoints due to human papilloma virus infection. Over 90% of cervical cancer patients are infected by this virus and thus most cervical cancers are partially defective in cell cycle checkpoints and cell division. Cervical cancer cells are more reliant on the remaining way of cell division control, namely the G2/M checkpoint, for survival. New strategy has been developed to inhibit the G2/M checkpoint and thus pushes the cervical cancer cells towards defective cell division and death. The target of our investigation, Myt1, is one such G2/M checkpoint regulator. A drug has been developed against Myt1 and is very effective in pushing cervical cancer cells to defective cell division and cell death. However, some cancer cells can survive or are resistant to the Myt1 drug. The objective of the proposal is to understand how cervical cancer cells can survive treatment of the Myt1 drug so that we can use it effectively in the clinic. When the G2/M checkpoint is inhibited, cancer cells have defective cell division and very often result in broken and shattered chromosomes and most cells cannot survive. In the past, scientists thought that these shattered chromosomes cannot be repaired. Recently, cells were found to be able to repair even shattered chromosomes during cell division and thus promote survival. In the second objective, we will examine how we can prevent these shattered chromosomes from getting repaired. We propose that inhibition of repair will enhance cancer cell killing and can be used in combination with the inhibition of the G2/M checkpoint (such as using the Myt1 drug). Our proposal will allow better understand of cervical cancer cells can survive treatment and potentially lead to new treatment strategies and improve patient survival.