Beth Israel Deaconess Medical Center Boston, Massachusetts
Associate Professor and Attending Physician, Harvard Medical School
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 are seeking strategies to improve treatments for women with metastatic breast cancer. To accomplish this, they are testing combination therapies, and seeking biomarkers that can predict responses. The results of these studies will ultimately be translated to the clinic to improve the survival of patients with metastatic TNBC.
PARP inhibitors are helpful in BRCA-driven breast cancers, but they may also be useful in other patients with DNA-repair deficiencies—it is just a matter of finding those patients. To that end, the team developed a new mutational signature that may identify patients who are deficient in DNA repair, even in the absence of inherited BRCA mutations. The team also further explored the effects of PARP inhibitors on the immune system and found that these therapies reprogrammed a subset of immune cells to be tumor-targeting. This PARP inhibitor-induced anti-tumor activity could be further enhanced by the addition of an immune-promoting combination therapy.
The Wulf team will investigate a combination therapy of olaparib and the PI3K inhibitor alpelisib in a randomized study in recurrent TNBC, to provide a definitive answer as to whether this combination is better than olaparib alone, and whether patients without a BRCA mutation can benefit from this strategy. They will also validate their mutational signature that identifies patients whose tumors are DNA repair-deficient and could benefit from PARP inhibitors. In addition, they will continue their studies of how PARP-inhibitors reprogram the immune system, in pursuit of new targeted therapies.
“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 has collaborated closely with Dr. Lewis Cantley (who discovered the PI3 kinase pathway) to develop and test preclinical models for assessing novel combination treatments that include the use of a PI3Kinase inhibitors.
2011
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