Tan A. Ince, MD, PhD
New York, New York
Professor of Pathology and Laboratory Medicine
Chief of Pathology, NewYork-Presbyterian Brooklyn Methodist Hospital
Weill Cornell Medicine
New York, New York
Uncovering what drives aggressive versus slow-growing tumors for more personalized treatments for breast cancer.
Cancer is often caused by oncogenes–genes that when mutated or abnormally expressed (turned on when they should not be) drive the development of cancer. Oncogenes may behave very differently in different breast cells. In some breast cells, an oncogene may generate highly aggressive and metastatic tumors, while in another type of breast cell, the same oncogene may create slow-growing tumors. Dr. Ince is working to explain what causes this cell-specific oncogenic effect, and whether it can be used as a prognostic indicator or therapeutic target.
Dr. Ince discovered several proteins that regulate how oncogenes interact with DNA to promote aggressive tumor development. In contrast, they discovered that receptors for estrogen, androgen, and Vitamin D (ER, AR and VDR, respectively) found on some normal breast cells regulate cancer stem cells, which can give rise to tumors, and slow or prevent tumor growth. When found together, ER, AR, and VDR are a powerful predictor of positive outcomes.
Dr. Ince plans to test the idea that the proteins that enhance the effects of oncogenes also counter the functions of ER, AR, and VDR. This research could reveal prognostic or therapeutic targets that could ultimately be used to predict outcomes and develop novel treatments for breast cancer.
Dr. Ince received his PhD in Pharmacology from Cornell and completed clinical training at Massachusetts General Hospital, Brigham and Women's Hospital, and Harvard Medical School. Dr. Ince was a visiting clinical scientist at Massachusetts Institute of Technology, 2000-2007, where he developed a new cell culture nutrient medium that is now widely used to grow human breast and ovary cells. He is currently Chief of Pathology at New York-Presbyterian Brooklyn Methodist Hospital and a professor of pathology at Weill Cornell Medicine.
Dr. Ince's research focuses on the role of normal cell-of-origin in determining tumor phenotype and development of culture systems for in vitro culture of primary human tissues and tumors. The use of normal cell types as a reference to classify tumors, however, has not been widely emulated in solid tumors, partly due to a more limited understanding of epithelial cell differentiation. Dr. Ince used a new and innovative multiplexed immunofluorescence technology to monitor multiple markers simultaneously in the very same cells. Based on the study, Dr. Ince and colleagues described eleven new normal breast subtypes and showed that each human tumor is similar to one of these normal cell types. These results led to new normal cell type-based classification of breast cancers that has important implications for understanding breast cancer prognostics and how breast cancer is treated. In brief, the results of this study indicate that breast tumors arising from different normal cells have significantly different clinical outcomes and drug response and should be classified and treated differently.
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