Funded Research: 2018
Jocelyn Reader, Ph.D., Young Investigator
University of Maryland Baltimore .
Targeting the PGE2 EP4 receptor as a mechanism for improved chemotherapeutic response in epithelial ovarian cancer
Ovarian cancer is one of the most deadly gynecologic cancers. Inflammation: is associated with the development and progression of cancer including ovarian cancer. Cyclooxygenases are proteins involved in producing a molecule that can lead to inflammation. These proteins can be blocked with drugs called NSAIDS (non-steroidal anti-inflammatories) such as ibuprofen and aspirin. However, due to concerns of toxic side effects, we sought to use drugs to target a different protein called EP4. We propose that using drugs to block the EP4 protein called an EP4 inhibitor will lead to fewer toxic side effects. Currently, standard treatment for ovarian cancer includes surgery to remove cancer and chemotherapy to kill the cancer cells. Chemotherapy has toxic side effects and eventually cancer cells can become resistant to treatment and will no longer be killed by the chemotherapy. We propose to combine the EP4 inhibitor with chemotherapy to improve the effectiveness of this treatment. With this new combination, we may be able to make cancer cells more sensitive to the chemotherapy and reduce toxic side effects. Our goal is to use cell lines and mouse models in order to identify the best drug combination to use to treat ovarian cancer. We also want to discover features of the cancer cells that can be utilized in the future to identify patients that would most benefit from this treatment. The successful completion of this project will lead to a new type of combination therapy and will lead to the improvement of current ovarian cancer treatments.
Yaşuto Kinase, MD, PhD, Young Investigator
Ovarian Cancer Research Center University of Pennsylvania
Perelman School of Medicine Targeting Ovarian Clear Cell Carcinoma with Genomics and Better Models DOW
While clear cell carcinoma of the ovary is a relatively rare subtype of ovarian cancer, it is also the most difficult to treat in advanced stages. There are currently no effective therapies for women with this type of ovarian cancer and it represents a significant unmet medical need. Part of the failure to advance care in this area is that there are few, if any, model systems that recapitulate the features of the human disease. Our first aim will be to conduct a comprehensive molecular analysis of eight cell lines that are presumed to be clear cell carcinoma. Our analysis will reveal the specific types of mutations that these cell harbor and also determine which of these cell lines can grow in a mouse a formátumor that can be readily detected. Those that do might be ideal for future drug discovery efforts. Our second aim will utilize genomic technologies to elucidate how clear cell tumors arise, their relationship to endometriosis, and what underlies their propensity to be resistant to standard chemotherapy. This approach will rely on the robust tissue banking platform available at the Penn Ovarian Cancer Research Center. We will use special lasers to capture the early tumor cells in the ovary and compare their genetic make-up to the metastatic lesions in the abdominal cavity of these patients. The goal is to understand how these tumors arise and define vulnerabilities that will lead to new biomarkers of disease and drug targets.