Rationale: Ovarian cancer tends to come back after surgery and standard chemotherapy. To improve the outcomes of women afflicted with this deadly cancer, development of new treatments is very much needed. One new area of research that shows high promise is the use of drugs that boost the patient's immune system causing rejection of tumors and decrease of the cancer burden. Such treatments have recently entered the clinical arena in other malignancies and are being studied in ovarian cancer. Here we propose a novel modality to increase the effects of immune boosting treatments by combining them with drugs that unlock the genetic code and make the cancer cells more recognizable by immune cells. We will test these research objectives in tissues collected from women with ovarian cancer treated in a clinical trial with this new drug combination that we are conducting at Northwestern University.

Relevance of the research project to the mission of the Ovarian Cancer Research Program (OCRP): This research project is directly applicable to women with ovarian cancer, and the treatment tested can make a difference in their battle with this fatal illness. Thus, the proposal fits the mission of OCRP to "support patient-centered research to treat and cure ovarian cancer." Additionally, the proposed study is focused on improving effects of immunotherapy, which has been identified by the OCRP as one of the area of encouragement in the 2016 research program.

New paradigms in ovarian cancer: This research project proposes a new treatment for women with chemotherapy-resistant ovarian cancer that aims to increase the patient's own immune defense to reject the growing tumors. Thus, the new therapy could immediately help women who have failed standard chemotherapy and have limited options to extend their lives. The research will therefore address a key unmet need in ovarian cancer.

The proposed strategy is novel and could change the direction of the field of immune treatment in cancer. If the project is successful, the new treatment could be tested on a larger scale in women with ovarian cancer. The project will also find new tests that can monitor how the immune system reacts to treatment, thus improving selection of patients who are likely to benefit from immune-based treatment.

Research aiming to improve the outcome of fatal diseases affecting women, such as ovarian cancer, is also of particular significance to the military beneficiaries, because the number of women in the US Armed Forces has increased substantially from 2% in 1973 to 15% in 2002. In 2004, of 485,500 active Soldiers, 71,400 were women. Therefore, this clinically applicable project is highly significant to Service members and their families.