Targeting the Stem-Like Cells of Chemoresistant High Grade Serous Ovarian Cancer: BMI1 in the Spotlight

Despite frequent initial responses to platinumtaxane therapy, most patients with high-grade serous ovarian cancer eventually develop resistance that leads to low responsiveness to any drug and shortened survival. We and others, have demonstrated that the polycomb protein BMI1 mediates a molecular stem-like phenotype and reprograms cellular metabolism leading to chemo resistance. Our goal is to elucidate the link between mitochondrial and nuclear functions of BMI1 that lead to therapy resistance and also evaluate targeting of this axis using the clinically relevant inhibitors. We have identified post-translational modifications of BMI1 that may affect its stability and function as a transcriptional regulator. These modifications may be instrumental in mediating oncogenic activity of BMI1, which are being investigated.