Ovarian cancer is fifth highest cause of cancer deaths among women in the United States and the most lethal gynecologic malignancy. Most women initially respond to treatment, but then develop recurrent disease that becomes resistant to chemotherapy. Patients then undergo multiple subsequent treatment regimens in the effort to slow the disease, with an average of only four months on each treatment. These sequential therapies cause cumulative toxicity and decreased quality-of-life. Thus, new treatments are needed for women with ovarian cancer that have both increased efficacy and decreased side-effects. My laboratory focuses on understanding why ovarian cancers grow and spread, with the goal of identifying new treatment approaches that can ultimately be translatied to the clinical trial setting.
A primary area of our research is to understand the impact of DNA damage on the induction of immune responses. This work is funded through an R01 grant from the National Cancer Institute. Ovarian cancers are characterized by defective DNA damage repair. This inability to repair DNA damage effectively results in the development of new mutations in the DNA that can be identified by the immune system as “foreign.” Thus, the induction of DNA damage has the potential to sensitize tumor cells to immunotherapy approaches. Our team is working to understand how we can use medicines to block the non-homologous end joining (NHEJ) pathway of DNA damage repair in combination with immunotherapy.
Our second area of research is understanding estrogen hormone signaling in ovarian cancers, such that we can develop combination therapies with antiestrogen therapy that have a low side effect profile. Anti-estrogen therapy is often used for estrogen receptor (ER)-positive breast cancer, yet despite 80% of ovarian cancers expressing ER, response rates are only 20%. Interestingly, we have shown that in some women with ER-negative tumors, antiestrogen therapy can be effective. We seek to understand these contradictions between ER expression status and response rates, so that we can make AET more effective in ovarian cancer. We hypothesize that tumor microenvironment signals modulate responses to antiestrogen therapy, and targeting the tumor microenvironment pathways can improve treatment responses.