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H. Shelton Earp, MD
Lineberger Professor of Cancer Research
Director, UNC Cancer Care
Professor of Medicine & Pharmacology
University of North Carolina
Chapel Hill, North Carolina
Goal: To identify ways to improve the effectiveness of immunotherapy in breast cancer patients.
Impact: Dr. Earp has identified a gene, MerTK, that blocks the effect of immunotherapeutic agents. Inhibiting MerTK could be a means of enhancing immune reaction to the tumor cells.
What’s next: He and his team will investigate how MerTK stimulates immune suppression in breast cancer and whether MerTK inhibition can make other forms of therapy more effective.
While a promising form of treatment, immunotherapy has not been effective in most forms of breast cancer. Thus, new strategies are needed to improve response to these drugs. Dr. Earp and his team are working to uncover genes like MerTK that regulate both breast cancer growth and the body’s immune response to breast cancer so that more patients may benefit from immunotherapy.
Full Research Summary
Research goal: To uncover genes that regulate breast cancer growth and the body’s immune response to breast cancer.
Impact: Dr. Earp’s research is aimed at understanding the immune microenvironment in breast cancers. His work may identify novel strategies that could enhance the effectiveness of existing immunotherapy, which has had only modest benefit in breast cancer patients.
Current investigation: The team has been studying the Mer Receptor Tyrosine Kinase (MerTK) gene, which plays a complex role in breast cancer cell survival in certain tumors. MerTK activity in the normal immune cells surrounding the cancer can stimulate metastases to other organs. In the breast cancer microenvironment, MerTK sends immunosuppressive signals, preventing a robust immune reaction to the tumor cells. Dr. Earp hopes to determine whether inhibiting MerTK could create a strong, anti-tumor immune response.
What he’s learned so far: Dr. Earp’s research has shown that laboratory breast cancer models evolve to recruit immunosuppressive cells into the tumor bed. He and his team have also found that circulating immune cells in the blood of patients with metastatic triple negative breast cancer (TNBC) have higher levels of MerTK than immune cells from healthy patients.
What’s next: The team will continue genetic and pharmacologic experiments to uncover the mechanisms by which MerTK stimulates immune suppression in breast cancer, as well as determine whether MerTK inhibition can make other forms of therapy more effective.
Shelton Earp is the Lineberger Professor of Cancer Research, Director of UNC Cancer Care and former Director of the UNC Lineberger Comprehensive Cancer. In these roles, he has helped develop basic, clinical and public health research and cancer care at one of the country’s premier public universities and academic medical centers. He serves as Principal Investigator of the UNC Breast Cancer SPORE and his laboratory conducts fundamental and translational research in breast cancer and childhood leukemia. His group has discovered and studied genes involved in a range of cancers, published over 160 biomedical-research articles and been continuously funded by NIH for over 35 years. He is currently collaborating with the UNC Chemical Biology Center in the Eshelman School of Pharmacy to develop a new, first-in-class drug targeting one of the cancer genes discovered in his lab. Inhibition of this gene may stimulate a breast cancer patient’s innate immunity against their cancer.
Dr. Earp has received UNC School of Medicine teaching awards and chaired national review committees for the American Cancer Society and the National Cancer Institute. He has served as President of the American Association of Cancer Institutes, on the NCI Board of Scientific Advisors, and on the advisory boards of ten university cancer centers. His lab is supported by NIH grants, the Breast SPORE and the Breast Cancer Research Foundation.