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Mark Pegram, MD
Susy Yuan-Huey Hung Professor
Director, Breast Cancer Program
Co-Director, Translational Oncology Program,
Associate Director for Clinical Research
Stanford Cancer Institute
Stanford University, School of Medicine
Seeking strategies to prevent drug resistance and improve outcomes for patients with HER2-positive breast cancer.
A novel experimental model system is employed to identify pathways driving resistance to HER2-targeted drugs.
These innovated studies will accelerate the discovery of new treatment for pateints with advanced HER2 breast cancer.
Many therapeutic antibodies, like Herceptin®(trastuzumab) bind to cell surface receptors and block signaling pathways inside cells to inhibit cell division and growth. In addition, the antibodies recruit and activate immune cells called natural killer cells to the tumor sites and elicit a tumor-killing process called antibody-dependent cell-mediated cytotoxicity (ADCC). Hence, tumor cells face selection pressures from both the antibodies and the immune effector cells.
Most studies on antibody resistance have been conducted in the absence of immune effector cells, thus ignoring important mechanisms of resistances.
Dr. Pegram and team have recently developed an experimental model to artificially create antibody-resistant HER2-positive breast cancer cells. Utilizing this model, they will investigate the possible mechanism(s) of tumor cell resistance to Herceptin® in the presence of natural killer cells.
The long-term goal of this study is to characterize this resistance and identify potentially new resistance pathways or markers that can be targeted with a drug.
Mark D. Pegram, MD is a renowned clinician and scholar in breast cancer research and a leader in translational medicine. Dr. Pegram played a major role in developing the drug Herceptin as a treatment for HER2-positive breast cancer, which constitutes about 20 percent of all cases. His laboratory experiments demonstrated that combining Herceptin with chemotherapy effectively killed cancer cells that overproduced the growth factor HER2. Dr. Pegram and others then conducted clinical trials showing that Herceptin improved survival rates and even cured some breast cancer patients. This remains one of the premier examples of bench-to-bedside translational research. Dr. Pegram’s current research efforts include a continued focus on the cancer-associated gene that encodes HER2 and developing new ways to target cancer cells expressing this protein. He is also pursuing strategies to target estrogen receptors, implicated in some 70 percent of all breast cancer cases.
BCRF Investigator Since