Recent studies have shown that women with ovarian cancers that result from an inherited mutation in the BRCA gene, show an excellent response to a drug called a PARP inhibitor. This is because the drug capitalizes on a vulnerability created by the gene mutation, allowing it to kill cancer cells and spare normal cells.
We have found an additional vulnerability in these hereditary ovarian cancers that stems from the response of the immune system to the tumors. Studies have demonstrated that in some women with ovarian cancer, immune cells naturally attack the tumor and this improves survival. Women with ovarian cancer that results from an inherited syndrome are more likely to show evidence of an immune attack on their tumor. As a result, these women may be the best candidates for therapies that enhance the immune response to cancer cells.
We attribute the robust immune response elicited by hereditary tumors to a defective DNA repair system that is caused by the BRCA gene mutation. PARP inhibitors disable a second DNA repair system, resulting in the selective destruction of cancer cells. We predict that this drug also enhances the anti-tumor immune response, which contributes to its therapeutic effect. We plan to test this, and to combine the PARP inhibitor with a drug called anti-CTLA4 antibody, which increases the ability of immune cells to kill tumor cells. We expect that this combination will have a powerful therapeutic effect by increasing the number and diversity of immune cells travelling to the tumor, and then enhancing their ability to destroy tumor cells once they encounter them.
Because many non-hereditary ovarian cancers also develop defects in BRCA function, we expect that the results of this study may apply to a large proportion of women with ovarian tumors.
Dr. Sarah Adams joined the faculty of the University of New Mexico Cancer Center in 2102, where she is an Assistant Professor, and the Victor and Ruby Hansen Surface Professor in Ovarian Cancer Research in the Department of Obstetrics and Gynecology. Prior to her recruitment to the University of New Mexico, she spent several years at the University of Pennsylvania. Her undergraduate degree is from Harvard University, and she completed medical school and a residency in obstetrics and gynecology at the University of Chicago. In addition to being a skilled physician, Dr. Adams is also an accomplished researcher. She is a 2011 recipient of OCRA’s prestigious Liz Tilberis Award. In addition to OCRA, her work has been supported by grants from the Gynecologic Cancer Foundation, the Sandy Rollman Foundation, the Kaleidoscope of Hope Foundation, the Ovarian Cancer SPORE through the Fox Chase Cancer Center, and the American Society of Clinical Oncology with a Young Investigator’s Award.
Dr. Adams’ overarching research interest is the investigation of the immune response to ovarian cancer, and the interaction of this response with immunomodulatory effects of chemotherapeutic regimens used for treatment. Her current research is focused on exploiting the specific vulnerability of hereditary ovarian cancers to immune attack to develop targeted combinatorial therapeutic protocols for women with tumors arising as a result of BRCA gene mutations. Based on evidence that many sporadic tumors lose BRCA function, she expects that the results from this work may be used to improve the treatment of a large proportion of women with ovarian cancer.