Beth Israel Deaconess Medical Center Boston, Massachusetts
Associate Professor and Attending Physician Harvard Medical School
Identifying novel treatment combinations 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 team aims to translate the studies’ results to the clinic to improve the survival of patients with metastatic TNBC.
PARP inhibitors are approved for treatment of BRCA-driven breast cancers, but they may also be useful in other patients. Dr. Wulf and her team have discovered that mutations in KMT2C, a tumor-suppressing gene which can drive a greater likelihood of metastasis, are sensitive to PARP inhibitors. Dr. Wulf and her team found that removing KMT2C using the CRISPR/CAS9 tool made cells more sensitive to PARP inhibitors and helped reduce the spread of cancer. In other studies, Dr. Wulf is investigating SHP2 inhibitors since SHP2, an enzyme that plays a role in several cancer-related pathways, is currently being investigated as a target for cancer treatments. Prior studies revealed that using PARP and SHP2 inhibitors together can be very effective in treating breast cancer. In their laboratory models of BRCA1-related breast cancer, the team confirmed the strong benefits of this combination in shrinking tumors in both BRCA1/BRCA2 mutant and non-mutant breast cancer models.
Dr. Wulf will continue to test treatment options that specifically target DNA damage repair mechanisms. This includes testing PARP-inhibitor combination therapies on KMT2C mutant models in the laboratory and potential clinical trials further investigating KMT2C-mutant breast cancer. They will also build on their work with SHP-2 inhibitor plus PARP inhibitor, screening cell lines to find sensitive and resistant lines to decipher what contributes to resistance. In addition, they will experiment with DNA damage repair assays to assess whether SHP2 inhibition induces DNA damage. Through her translational work, Dr. Wulf and her team are identifying new biomarkers and pursuing combination therapies that can improve treatment responses and provide new treatment options to patients.
Gerburg Wulf, MD, PhD 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 BCRF Investigator 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 PI3K inhibitors.
2011
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