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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 such as PARP- and P13K-inhibitor combinations which have shown some success in TNBC. They will also investigate the role of the tumor immune microenvironment in response to these therapies.
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 fewer treatment options, but also face a high likelihood that their cancer will spread—a process called metastasis. Once breast cancer has spread, it is considered incurable. Dr. Wulf and her colleagues, including 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- 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 metastatic TNBC patients.
Current research: Dr. Wulf and her team are conducting studies to discover biomarkers from circulating tumor (ct)DNA that are associated with treatment response to combination therapy with PARP-inhibitor, Olaparib, and P13K-inhibitor, alpelisib. They will also investigate the elements of the tumor immune microenvironment that affect response to this combination strategy.
What she’s learned so far: Dr Wulf’s team has completed a multi-institutional early phase clinical trial testing the combination of PARP-inhibitor, Olaparib, and P13K-inhibitor, Alpelisib, in TNBC patients. They found that 36 percent of patients achieved a partial remission and 50 percent disease stability. Further clinical trials in breast and ovarian cancer are being planned. In other studies, her team found that ctDNA is a promising biomarker of response – ctDNA can be detected in blood samples from patients. In addition, they have found that 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 determine if genomic alterations found in ctDNA can predict and monitor response to Olaparib or the combination of Olaparib and Alpelisib. They will also determine ways to improve the efficacy of the PARP/P13K- inhibitor combination and to 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.