Titles and Affiliations
Emil Frei III Professor of Medicine
Director, Center for Functional Cancer Epigenetics
Research area
Improving immunotherapy in triple-negative breast cancer.
Impact
Triple-negative breast cancer tumors do not have estrogen, progesterone, or HER2 receptors commonly found in breast cancer. While traditional chemotherapy and newly developed immunotherapies are successful in treating some patients with TNBC, it is an aggressive breast cancer subtype, and many patients succumb to the disease. This is partly driven by the fact that TNBC tumors are very heterogeneous, so no single therapy will be effective for all patients.
Dr. Brown is working to find new and effective treatments for TNBC including combination targeted therapies and immunotherapy. His work on immune response to TNBC grew out of studies aimed at understanding the detrimental effects of obesity on TNBC outcomes. Researchers currently don’t fully understand how obesity-driven changes to breast fat tissue regulate the immune response in TNBC. The goal of his work is to elucidate the mechanism by which obesity suppresses anti-tumor immunity, with the hope of improving immunotherapy in TNBC.
Progress Thus Far
Dr. Brown and his team are using laboratory models to study fat and tumor cells on the single-cell level. In studying obesity in laboratory models of TNBC, his team has shown immune cells present in the mammary gland of obese subjects alter how fat tissue processes and uses lipids in a way that suppresses cancer-fighting immune cells. Additionally, the team has found that tumor growth with weight loss induced by diet or treatment with tirzepatide, a GLP-1 based medication used to treat type 2 diabetes and promote weight loss. It remains unclear whether tirzepatide slows tumor growth directly or by reshaping the immune environment around the tumor.
What’s Next
In the coming year, the team will further explore the mechanism by which weight reduction restores the immune system’s ability to control tumor growth and will test whether tirzepatide’s anti-tumor effect depends on reversing these obesity-driven changes. This work aims to lay the groundwork for repurposing these widely used medications to improve breast cancer outcomes, particularly for patients affected by obesity.
Biography
Myles Brown, MD is Director of the Center for Functional Cancer Epigenetics at Dana-Farber Cancer Institute (DFCI) and Emil Frei III Professor of Medicine at DFCI and Harvard Medical School. He obtained his BS in Biology from Yale and his MD from Johns Hopkins University School of Medicine. Following training in internal medicine at the Brigham and Women’s Hospital, a fellowship in medical oncology at the Dana-Farber and postdoctoral research at MIT, he joined the staff of the Dana-Farber Cancer Institute and the faculty of Harvard Medical School. Dr. Brown’s research is focused on understanding the factors underlying the hormone dependence of breast and prostate cancers. He is recognized for three seminal discoveries including the role of p160 co-activators in steroid receptor action, the dynamic nature of co-regulator function, and the predominance of steroid receptors as enhancer rather than promoter-binding factors. He is a member of the National Academy of Medicine, the National Academy of Sciences and Fellows of the American Academy of Cancer Research (AACR), the American Academy of Arts and Sciences, and the American Association for the Advancement of Science (AAAS). He is on the Editorial Board of the Proceedings of the National Academy of Sciences.
