H. Shelton Earp, MD
Professor and Director, Lineberger Comprehensive Cancer Center
Professor of Medicine and Pharmacology
University of North Carolina, Chapel Hill, NC
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The UNC Lineberger team continues its tripartite research program featuring clinical and genetic breast cancer research, and is currently focused on three projects: A New and Improved Anti-HER2 Breast Cancer Vaccine; Complex Genetic Determinants of Breast Cancer Etiology and Response to Therapy; and EGF Receptor Family in Breast Cancer: The Role of HER4. Progress has been made in all three projects. The anti-HER2 cancer vaccine trial testing a new way of preparing patient's immune cells continues to accrue patients. The studies of the HER4 gene in breast cancer has resulted in publications that show HER4 can send both tumor promoting and tumor suppressive signals depending upon the HER4 gene variant present. Further studies to understand the mechanisms of these opposing HER4 actions are planned.
Phase I/II trials continue, investigating the combination of vinorelbine, trastuzumab and a multi-epitope dendritic cell vaccine in the treatment of women with high HER2-expressing metastatic breast cancer. An FDA-approved change in the method for creating the vaccine immune cells has been instituted in the last three patients enrolled; thirteen women are now on the trial.. This change resulted in the strongest anti-HER2, T-cell immune response the researchers have observed.
The second project has entered over 1,400 women (~790 with breast cancer and 630 matched women without breast cancer), obtaining blood for germline DNA extraction, as well as epidemiologic, clinical, therapeutic, and outcome data for translational studies aimed at understanding how complex genetic inheritance influences a woman's predisposition to breast cancer and her response to therapy. In the third project, the researchers are studying the fourth member of the EGF receptor family, HER4. There are two variants of HER4 that differ by a small stretch of amino acids in the part of the protein that goes to the nucleus. Their recent data demonstrate that the Cyt1 variant slows breast cancer cell growth and causes breast cell differentiation. The other isoform (Cyt2) actually stimulates growth. They hope to unravel the mechanisms by which these two HER4 variants (which differ by only 16 amino acids) have diametrically opposing actions. They also hope to determine the ratio of the two isoforms in human breast cancers and correlate that with the patient's clinical course.
Mid-Year Progress Report:
The Phase I/II anti-HER2 cancer vaccine trial testing a new way of preparing patient's immune cells continues to accrue patients; 17 women have enrolled to date. The Linberger Cancer Center's studies of the HER4 gene in breast cancer have resulted in publications that show HER4 can send both tumor promoting and tumor suppressive signals depending upon the HER4 gene variant present. Further studies to understand the mechanisms of these opposing HER4 actions are underway.
Bio:
Shelton Earp is a 1970 graduate of the University of North Carolina School of Medicine. After a medical internship at Vanderbilt and service in the army, he returned to Chapel Hill where he performed his residency and fellowship, joining the faculty in 1976. He is now the Lineberger Professor of Cancer Research and a professor in the Departments of Medicine and Pharmacology. In his role as Director at the UNC Lineberger Comprehensive Cancer Center, he coordinates cancer research and care at one of the country's premier public universities, including establishment of cancer epidemiology and prevention research programs with faculty in the School of Public Health.
His own laboratory conducts clinical and translational breast cancer research as well as basic research on the behavior of cancer cells by studying the signals that regulate cell growth, differentiation and programmed cell death. His group has identified and studied genes involved in these cellular decisions. He has authored 120 biomedical-research papers and has recently received a new R01 grant, in addition to serving as Principal Investigator of the UNC Breast Cancer SPORE and UNC Lineberger Comprehensive Cancer Center grants. The UNC Breast SPORE, one of the original four Breast Cancer SPOREs, was just renewed for five years, Years 15-19.
Dr. Earp has been the recipient of UNC School of Medicine teaching awards and has served on boards and chaired national review committees for the American Cancer Society and the National Cancer Institute. He is an elected member of the American Association of Professors, the American Society of Clinical Investigation, and was recently elected to the board and as President of the American Association of Cancer Institutes. He is a recipient of The Breast Cancer Research Foundation funding for work to develop breast cancer vaccines, to understand the genetic predisposition to breast cancer, and to investigate breast cancer tumor suppressor function.
