Grantee: Cecil Han, PhD
Institution: Georgetown University in Washington, DC
Area of Focus: Biochemistry and Immunology of Cancer
Grant Term: 01/01/2022-12/31/2025
“About 75% of epithelial ovarian cancers are high-grade serous carcinomas. These cancers are complex and variable, making them difficult to treat. In earlier studies, my lab learned that blocking the protein USP13 causes ovarian cancer cells to die and the growth of tumors to dramatically slow. So we developed a new mouse model to allow us to better study the role of USP13 protein in epithelial ovarian cancer.
“USP13 is barely present in a non-cancerous ovary or fallopian tube, but it’s present at high levels in ovarian cancers — and high levels of USP13 are linked with poor survival. With our mouse model, we demonstrated that USP13 enhances the development, growth, and spread of high-grade epithelial ovarian cancers. In the future, we hope to develop a specific USP13 inhibitor to treat ovarian tumors with high level of USP13. We also hope to identify and learn about other targets to overcome metastasis and chemotherapy resistance in these deadly ovarian tumors.”
The Challenge: About 90% of women diagnosed with ovarian cancer have epithelial ovarian cancer. This type of cancer starts on the outer surface of the ovary and has few established risk factors and the worst prognosis. It’s the deadliest type of gynecological cancer. Overall survival rates for people with epithelial ovarian cancer have not changed over the past 30 years.
Many genes work together to control how a tumor forms, grows, and spreads (metastasizes). Discovering the specific roles each gene plays in cancer cells can reveal new targets for treatment and eventually to the development of a new drug.
One potential tumor-promoting gene, USP13, contains the information to make an enzyme that has been found at high levels in this type of ovarian cancer, and that enzyme appears to be critical for epithelial ovarian cancer cells to survive and grow. USP13 has been studied for normal cell functions, but its roles in the development of this type of ovarian cancer and its progression are not known.
The Research: To study the role of USP13, American Cancer Society (ACS) research grantee Cecil Han, PhD, and colleagues developed a new genetically engineered mouse model (GEMM) that has similar features as high-grade serous epithelial ovarian cancer in people. She published their learnings from this mouse model in Nature Oncology.
Han’s team found that high levels of the enzyme USP13 promoted the formation of highly aggressive tumors that quickly metastasized, causing a shorter survival time. To their knowledge, no one has previously reported the ability of USP13 to do that.
These findings reveal USP13 as a potential new target for drugs to treat ovarian cancer.
Why it Matters: Han, as well as other scientists, now have a mouse model with similar genetic defects, structure, and behavior as epithelial ovarian cancer in women. She and other researchers may use this model to continue to study the role of the USP13 gene and others to learn more about the disease. They can also use the model to evaluate chemotherapy and targeted therapy strategies to treat ovarian cancer.