Angela Russo, Ph.D
University of Illinois at Chicago – UIC
Chicago, IL, United States
2018 MARLYS CHENEY PILOT AWARD
Project: Characterization and targeting the markers of stemness altered during ovarian cancer pathogenesis using WNT inhibitors
Research Areas: Cell Biology, Stem Cells, Tumor Microenvironment
High-grade serous ovarian cancer is the most common type of ovarian cancer with the highest mortality rate. The lethal nature of these tumors is mainly due to the difficulty in detecting the disease at early stages when it is more treatable. Reduced amounts or absence of a protein called PTEN in fallopian tube cells is enough to lead to formation of a tumor and growth of tumor cells in the abdominal cavity. Dr. Russo’s research will aim to identify the cellular pathways that are turned on when this critical PTEN protein is lost in fallopian tube in order to identify early targets during the development of ovarian cancer. Dr. Russo’s preliminary experiments show that changes in a cellular pathway that involves the WNT protein and changes in “stemness” (giving ordinary cells properties of stem cells that have the potential of changing into many different kinds of cells) are involved in this process. Dr. Russo has shown that inhibiting function of WNT pathways with a drug called LGK-974 can reduce cancer cells from colonizing in the ovary. Importantly, the LGK-974 drug is in clinical trial for pancreatic and breast cancer, but not ovarian cancer. This work may set the ground work a potential approach for treating ovarian cancer patients with this drug. In this study, Dr. Russo aims to extend the use of the WNT inhibitors alone and in combination with chemotherapy drugs to test if the treatment blocks tumor metastases. Additionally, Dr. Russo will identify changes in cancer stem cells markers during ovarian cancer progression and determine whether WNT inhibitors reduce the expression of these markers. This work may help provide evidence to stratify the use of WNT inhibitor therapy based on the amount of PTEN expression and the make-up of cancer stem cell markers expressed in cancer cells.