Titles and Affiliations

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

Research area

Improving treatments and outcomes for patients with HER2-positive breast cancer.

Impact

The discovery of Herceptin® (trastuzumab) has dramatically improved outcomes for many patients with HER2-positive breast cancer. Despite this advance, up to 25 percent of women who initially respond to Herceptin® will experience a breast cancer recurrence within 10 years. Dr. Pegram is studying a pathway that blocks anti-tumor immune system activity. Restoring this immune response in combination with targeted therapies may lead to breakthroughs for those with advanced HER2-positive breast cancer.

Progress Thus Far

Dr. Pegram discovered that HER2, which is expressed at high levels in HER2-positive breast cancer, inhibits a signaling pathway called STING, an important component in activating the body’s anti-tumor response. He and his team have developed an innovative approach to re-activate the STING pathway in HER2-positive breast cancer cells to generate a tumor-specific immune response. 

What’s next

Reactivation of the STING pathway is a promising therapeutic approach but has not advanced to clinical application thus far. Dr. Pegram is continuing to develop strategies that combine the reactivation of STING with immune checkpoint inhibitors to elicit a strong immune response, generating powerful, tumor-specific T cells that eliminate breast tumor cells from the body. Their goal is to make immunotherapy a more viable treatment option for patients with breast cancer.

Biography

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

2013

Areas of Focus