Stanford University School of Medicine
Suzy Yuan-Huey Hung Endowed Professor of Medical Oncology
Medical Director, Clinical/Translational Research Unit
Associate Dean for Clinical Research Quality
Developing and testing novel therapies to improve outcomes for patients with triple-negative breast cancer.
Receptors are cell proteins that act like antennas to receive and transmit signals to instruct cells when to grow and divide and, most importantly, when to stop. Ligands are circulating proteins that bind to receptors and turn them on. Some tumors can hijack receptors and/or ligands so that receptors become stuck in the “on” position—this leads to uncontrolled cell growth, a hallmark of cancer. Two ligands, oncostatin M (OSM) and leukemia inhibitory factor (LIF), have been implicated in poor breast cancer outcomes when present in high levels, presumably by activating specific receptors. Dr. Pegram is conducting laboratory studies to determine whether either of these are viable targets for breast cancer treatment. Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with few treatment options and high mortality rates. Therefore, Dr. Pegram is focusing his investigations on TNBC and hopes his studies will lead to the development of a first-in-class therapy to expand the treatment options for patients with TNBC that currently have limited targeted therapies.
OSM and LIF are both prominent secreted factors in breast cancer and share a common receptor called gp130. Dr. Pegram hypothesizes that a gp130 receptor decoy could inhibit both ligands and provide a novel and attractive treatment approach, particularly for TNBC, that is potentially more effective than targeting either ligand alone. His team is engineering a gp130 receptor decoy to sequester OSM and LIF, preventing them from binding and activating their native receptors on breast cancer cells. In the next year, they will test their gp130 receptor decoys in preclinical experiments in hopes of advancing it into phase I clinical trials.
Mark Pegram, MD is the Suzy Yuan-Huey Hung Endowed Professor of Medical Oncology at the Stanford Comprehensive Cancer Institute, Associate Dean for Clinical Research Quality, and Medical Director of the Clinical Translational Research Unit at Stanford University School of Medicine. He is a renowned clinician and scholar in breast cancer research and a leader in translational medicine and played a major role in developing the drug Herceptin® as a treatment for HER2-positive breast cancer. 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 research efforts have been focused 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. Dr. Pegram is an expert in pre-clinical and early clinical development of oncologic therapeutics, with a focus on breast cancer. Recently, Dr. Pegram has turned this extensive experience in translational research and drug development towards addressing hard to treat TNBCs.
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