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BCRF Grantee Since


Donor Recognition

The Celebrity Cruises Award

Area(s) of Focus

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
Stanford, California

Current Research

In order to survive, grow and spread, breast cancer cells must produce an abundance of growth-promoting proteins. Many of these proteins–called oncoproteins–are present on the surface of the cancer cells, such as the HER2 receptor, and have been used as targets for therapy. Many others, however, are inside of the cells and are not easily targeted by current drugs. An alternative approach to breast cancer treatment would be to prevent or stop the production of these oncoproteins to make cancer cells more sensitive to anti-cancer drugs. Dr. Pegram and his colleagues discovered a unique feature in the way cancer cells produce oncoproteins, a process called alternative protein translation. In the last year they identified several proteins (called ITAFs) that are present at higher levels in breast cancer cells than in healthy cells, and found that they help the cancer cells grow, multiply, and resist drugs thorugh this alternative translation method. They are in the process of scrutinizing patient data to identify which subytpes of breast cancer are the most likely to benefit from drugs targeting ITAF proteins. In particular, several of the proteins seem to be enhanced in triple-negative breast cancers. Based on their studies so far, it appears that breast cancer cells are adept at moving/ trafficking ITAF proteins within the cell, and utilize this property to survive and grow. Dr. Pegram’s team will use advanced protein analysis techniques to determine precisely how the cancer cells accomplish this. Understanding the specific changes that cancer cells make to utilize ITAF proteins may provide new strategies for the development of targeted therapies in the future.


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.