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Gerburg Wulf, MD, PhD
Harvard Medical School
Beth Israel Deaconess Medical Center
Goal: To identify new treatment targets for metastatic triple negative breast cancer (TNBC).
Impact: Dr. Wulf is conducting laboratory and clinical studies to understand how TNBC tumors resist certain anti-cancer therapies and to discover biomarkers of response. This work may lead to the development of novel drug combinations that will improve outcomes for patients who have this aggressive subtype of breast cancer.
What’s next: Her team will continue to pursue strategies for improving response to targeted therapies. They also aim to identify mechanisms of resistance and responsiveness to treatment with a class of drugs called PI3K inhibitors, which have shown some success as a targeted therapy for TNBC.
TNBC is an aggressive form of breast cancer that is more likely to recur and spread (metastasize). Unfortunately, it is difficult to treat because TNBC lacks three important receptors—estrogen, progesterone, and HER2—that are used as targets for most breast cancer treatments. Dr. Wulf is testing combination strategies to improve response to a class of drugs used to treat TNBC, called PARP inhibitors.
Full Research Summary
Research area: Identifying novel treatment strategies for patients with triple negative breast cancer.
Impact: TNBC is an aggressive form of breast cancer. Patients with TNBC not only have few treatment options, but also face a high likelihood that their cancer will spread – a process called metastasis. Once breast cancer has spread, it becomes incurable. Dr. Wulf and her colleagues, including BCRF researcher, Dr. Lewis Cantley, are seeking strategies to prevent drug resistance and extend survival for patients with TNBC.
Current research: The research team is testing combinations of novel targeted inhibitors to disrupt tumor cell metabolism and growth promoting signals simultaneously to improve response to a call of drugs called PARP inhibitors, a promising therapy for TNBC.
What they’ve learned so far: Dr Wulf’s team has made significant progress in their laboratory studies including the following findings:
- TNBC cells are uniquely addicted to carbohydrates to build new cancer cells. They can block tumor cells growth in the laboratory with PI3K-inhibitors
- Circulating tumor(ct)DNA is a promising biomarker for responsiveness to this combination
- The PARP-inhibitor Olaparib has powerful effects on the tumor microenvironment, and specifically recruits specialized killer T-cells to the tumor
What’s next: In the coming year they will continue to advance these studies to:
- Improve the efficacy of the anti-PI3K/PARP combination
- Harness the immune stimulatory effects of PARP inhibitors to improve their efficacy in clinical trials
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.