Associate Professor, Harvard Medical School
Attending Physician, Beth Israel Deaconess Medical Center
Triple negative breast cancer (TNBC) is a type of breast cancer that lacks the estrogen/progesterone receptors and the HER2 protein. While TNBC is less common than estrogen receptor-positive (ER+) breast cancer, it is a particularly aggressive form of the disease, for which there are no targeted therapies. Dr. Wulf is working closely with BCRF colleagues Lewis Cantley (Weill Cornell Medical College) and Ursula Matulonis (Dana-Farber Cancer Institute) in the development and testing of new drug combinations that may improve outcomes in TNBC. These collaborative endeavors include genomic analyses of biopsies and specimens obtained from an ongoing Phase I clinical testing a new targeted therapy in patients with triple negative breast cancer or advanced ovarian cancer (led by Dr. Matulonis) as well as testing novel combinations in laboratory models of TNBC, in collaboration with Dr. Cantley.
The clinical trial has completed accrual of patients, and correlative studies are ongoing. The investigators reported a number of clinical responses and are now in the process of determining why some patients responded and others did not. They will focus on trying to find novel markers of responsiveness to this combination regimen. Such a marker would be highly valuable as it could identify patients who may benefit from a less toxic alternative to the standard chemotherapy.
In their laboratory studies, Drs. Wulf and Cantley are studying gene expression data to pinpoint mechanisms that may be causing the cancer cells to become resistant to anti-PI3K and PARP therapies, two new classes of targeted drugs in clinical trials of TNBC and BRCA1-associated breast cancers. Their current studies are focused on tumor metabolism and how anti-PI3K drugs interfere with energy production in cancer cells. They have identified a novel and possibly ancient mechanism that cells use to adapt their metabolism in response to their environment. Signals from the microenvironment induced by blocking the PI3K pathway will reshape the cytoskeleton, causing activation of metabolic enzymes that promote tumor cell survival. Their research will elucidate the biophysical and molecular mechanisms of this process, which may be aberrant in cancer, and can possibly be targeted for cancer treatment.
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.