In Vivo Treatment of Established HGSOC Line Using Novel Therapy
Mentor: Daniela Dinulescu, Ph.D. (Brigham and Women's Hospital)
High-grade serous ovarian cancer (HGSOC) is the deadliest, and most common, subtype of ovarian cancer. With a 5-year survival rate of less than 30%, HGSOC is one of the most malignant forms of gynecological disease affecting women in the United States today.1 As it has proven difficult to detect this type of cancer before it has metastasized, many studies have focused on the treatment of the disease in the form of several types of therapies. By testing these therapies in animal models, it is possible to assess their efficacy and toxicity in a safe environment before they are brought to clinical trial. Our collaborators at Brandeis University have created a novel compound, Flag C16, to be used to treat high-grade serous tumors through intravenous injections. In vitro studies and preliminary in vivo studies have already been conducted at Brandeis using the Flag C16 drug to treat mouse models injected with the HeLa cell line subcutaneously. We hope to further test the efficacy of this therapy by conducting a larger study using a mouse model of an aggressive ovarian cancer cell line. Using immune-deficient mice, we will inject them with an established HGSOC cell line (A2780) to create a more appropriate model for this therapy to be tested on. The therapy will be administered intravenously via intravenous injection. The efficacy of the drug will be monitored by imaging and weighing the mice. After three weeks of therapy, the mice will be sacrificed. Tumor samples will be collected, weighed, blocked, and stained with appropriate antibodies to assess their histology. The data collected during this study will help us to ascertain an appropriate use of Flag C16, taking into consideration the drugs safety, toxicity and efficacy, when treating HGSOC. Successful treatment of HGSOC in mice using Flag C16 would another step to bring a potentially lifesaving treatment option for women suffering with this disease to clinical trials. 1. National Cancer Institute. SEER (Surveillance, Epidemiology and End Results Program). SEER Cancer Fact Sheets: Cancer of the Ovary. [Accessed April 2017]. Available from: http://seer.cancer.gov/statfacts/html/ovary.html .
Figure 1. Toxicology Report of Flag C16 + Doxycycline IC50 values for therapy doxycycline + Flag C16, compared to free doxycycline for HeLa, HepG2, and MESA-DRX5 cells. HeLa, HepG2, and MESA-DRX5 all exhibited IC50 values of less than 0.5 M when treated with Flag C16 and doxycycline. When treated with just free doxycycline, HeLa, HepG2, and MESA-DRX5 exhibited IC50 values of 2.1 M, 3.1 M, and 2.5 M respectively. Consequently, all three cell lines demonstrated a decrease in IC50 with FlagC13 added, indicating increased potency with the novel compound. Source: