2011 Early Career Investigator Grant Recipient — Sarah Adams, MD

Sarah Adams, MD

University of Pennsylvania

Development of Combination Therapy with PARP-Inhibitors and Immunomodulation for BRCA1-Epithelial Ovarian Cancer

Project Summary

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.

Bio

Sarah Adams, MD, Professor and Fellowship Research Mentor, and OCRA's Scientific Advisor, graduated from University of Chicago Pritzker School of Medicine where she also completed her OB-GYN residency. She completed her GO fellowship at University of Pennsylvania Hospital in 2009 and stayed on as faculty at Penn with a research appointment in the Ovarian Cancer Research Center. Dr. Adams joined the UNM GO division in 2012 where she maintains active clinical practice and leads a translational research lab focused on ovarian cancer immunology. She is the Co-leader of the Cancer Therapeutics Research Program for the UNM Comprehensive Cancer Center P30 grant and the Associate Director of the Translational Science for the UNM Comprehensive Cancer Center. She is nationally recognized for her work in immunology of ovarian cancer and novel immuno-oncology clinical trials.