Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. EOC patients often develop chemoresistance, which inevitably leads to disease progression. Our research focuses on understanding the mechanism of the resistance to platinum-based treatment in ovarian cancer.
The protein P53 plays a central role in inducing cell death. Therefore, mutation caused inactivation of p53 can lead to chemoresistance. We discovered that even without mutations, in a unique population of ovarian cancer stem cells, wild-type p53 protein can aggregate into an inactive form, due to the deregulation of p53 protein degradation. This inactive form of p53 aggregates is similar to the amyloid fibrils that cause Alzheimer’s and Parkinson’s diseases. Our research will reveal the mechanisms of aggregated p53 protein causing chemoresistance and tumor progression. The proposed study will explain why patients without p53 mutations showed poorer survival and were more resistant to chemotherapies. We will also try to discover small molecules that can inhibit the aggregation of p53 protein as a new therapeutic approach to sensitize chemoresistant cancer cells to conventional therapies and to prevent recurrence and chemoresistance.