Gerburg Wulf, MD, PhD
Harvard Medical School
Beth Israel Deaconess Medical Center
To identify novel treatment targets for metastatic triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with few treatment options, and a high likelihood of spreading to other organs of the body—a process called metastasis. Once breast cancer has spread, it is considered incurable. Dr. Wulf and her colleagues, including long-time collaborator and BCRF researcher, Dr. Lewis Cantley, are seeking strategies to improve treatments for women with metastatic breast cancer. To accomplish this, they are testing the combination of PARP inhibitors and P13K inhibitors to kill cancer cells and/or modulate the tumor immune system to enhance the anti-tumor response. Moreover, they are seeking to discover biomarkers that can predict response to this combination therapy. The results of these studies will ultimately be translated to the clinic to improve the survival of patients with metastatic TNBC.
Dr Wulf's team has completed a multi-institutional early phase clinical trial to test the combination of PARP-inhibitor, Olaparib (Lynparza®), and P13K-inhibitor, alpelisib (Piqray® for treating TNBC patients. They found that 36 percent of patients achieved partial remission and 50 percent achieved disease stability—meaning the tumor did not grow. Through the analysis of the clinical trial data, her team focused on circulating tumor DNA (ctDNA, which can be detected in blood samples) to identify potential biomarkers of treatment response. From ctDNA analysis, they identified several candidate biomarkers, including a specific mutational marker that was associated with a good outcome.
In the coming year, they will continue to advance these studies and validate the potential biomarkers of response to olaparib or the combination of olaparib and alpelisib. They will also determine ways to improve the efficacy of the PARP/P13K inhibitor combinations and to harness the immune stimulatory effects of PARP inhibitors to improve their efficacy in clinical trials. Dr. Wulf hopes to find a combination that supports the anti-cancer activity of the PARP inhibitor while promoting immune-mediated destruction of tumor cells to obtain deeper and longer-lasting remissions.
"BCRF allowed us to pioneer the deep sequencing of circulating tumor DNA at a time when this was still considered exploratory and under development."– Dr. Wulf
Dr. Gerburg Wulf is an Associate Professor of Medicine at Harvard Medical School and an Attending Physician in the Breast Oncology Group at Beth Israel Deaconess Medical Center (BIDMC) and the Dana-Farber Harvard Cancer Center (DFHCC). She received her medical school and graduate training in Germany where she studied in Muenster and at the Max-Planck-Institute for Biochemistry in Munich. After a residency at the University in Heidelberg she came to the US in 1991 for a post-doctoral research fellowship in Hematology at Beth Israel Hospital. She received further post-graduate training at St. Elizabeth’s Medical Center (Internal Medicine) and at Beth Israel Deaconess Medical Center (clinical Hematology/Oncology), as well as a second post-doctoral fellowship in Cancer Cell Biology with Dr. Kun Ping Lu.
Her current professional work is a combination of clinical practice and laboratory-based research. As a board-certified oncologist, Dr. Wulf serves breast cancer patients from the greater Boston area in the Multidisciplinary Breast Cancer Clinic at BIDMC. She is an active clinical scientist and an NCI, ECOG and DFHCC investigator. Her focus is laboratory-based research where she is interested in novel treatment concepts for endocrine-resistant breast cancer. She is collaborating closely with Dr. Lewis Cantley, Director of the Cancer Center at Weill Cornell Medical School in New York, to develop and test in preclinical models novel combination treatments that include the use of a PI3Kinase inhibitors.
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