Grant: Project Grant

Epithelial ovarian cancer (EOC), which is the most common form of ovarian cancer, has the highest mortality rate of female cancers. The low survival rate for women with EOC results mainly from an inability to detect the disease at an early, curable stage and from the lack of effective treatment for advanced cancer. The Wnt/ß-catenin pathway is known to play critical roles in cancer development, such as maintaining the cancer stem cells, promoting the spreading of cancer cells from the primary tumor into other organs, and inhibiting the effectiveness of conventional chemotherapies. We, therefore, searched for novel inhibitors of this pathway and identified two compounds that have strong anti-tumor effects. The major objective of this project is to develop novel inhibitors that disrupt ß-catenin signaling as potential therapeutics for EOC patients who have high ß-catenin activities. We will further characterize the effect of these inhibitors on cancer stem cells, tumor growth, and metastasis. We will also investigate how these inhibitors disrupt ß-catenin signaling to exert their anti-tumor effects. Finally, we will generate structurally similar compounds to identify molecules that have better drug-like properties. The proposed studies will very likely lead to the development of novel targeted therapies for EOC. Since the Wnt/ ß-catenin pathway is involved in the development of many types of cancers, the small molecular inhibitors we develop will be useful for targeting a wide range of cancers.