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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 for treating 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: Identifying genes that regulate breast cancer growth and the body’s immune response to breast cancer which may be targeted to improve the efficacy of immunotherapy.
Impact: Immunotherapy has recently been used in the treatment of breast cancer with only modest benefit. Dr. Earp is examining the factors in the microenvironment of breast tumors that may be involved in suppressing a robust immune response in patients undergoing immunotherapy. His team discovered the MerTK gene which plays a complex role in breast cancer cell survival and metastasis. They showed that MerTK sends immunosuppressive signals that prevent adequate immune responses from patients which results in resistance to immunotherapy. He and his team are identifying novel strategies that could reverse the effects of MerTK and enhance the effectiveness of immunotherapy.
Current investigation: Characterizing the MerTK gene and determining whether inhibiting MerTK or genes like it could create a strong, anti-tumor immune response and improve the effectiveness of immunotherapy.
What he’s learned so far: In previous studies, Dr. Earp’s team has shown that breast cancers evolve to recruit immunosuppressive cells into the tumor bed. Moreover, they have discovered the MerTK gene which blocks the effect of immunotherapeutic agents and leads to therapy resistance. Conversely, they showed that deleting MerTK enhances the immune response, slows tumor growth and decreases metastasis. 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. His team has also identified an additional signaling molecule, Tyro3, that suppresses the immune response.
What’s next: Dr. Earp’s team will use both genetic and pharmacologic experiments to uncover the mechanisms by which MerTK and Tyro3 stimulate immune suppression in breast cancer, specifically TNBC. In addition, they will determine whether inhibition of these signaling molecules can make other forms of breast cancer therapy more effective. They hope to uncover additional genes like MerTK and Tyro3 that regulate both breast cancer growth and the body’s immune response to breast cancer so that more patients may benefit from immunotherapy.
Shelton Earp is the Lineberger Professor of Cancer Research, Director of UNC Cancer Care and 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 200 biomedical-research articles and been continuously funded by NIH for over 40 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.