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Tan A. Ince, MD, PhD
Live Tumor Culture Core and Tissue Bank Core Facility
Director, Tumor Stem Cell Division,
Interdisciplinary Stem Cell Institute
Associate Professor, Department of Pathology
University of Miami
Goal: To discover new approaches to target cancer stem cells and improve outcomes for patients with aggressive breast cancer.
Impact: Dr. Ince has identified a unique mechanism regulating breast cancer stem cells–the drivers in drug resistance and metastasis. His studies may reveal a non-chemotherapeutic approach to targeted therapy in aggressive breast cancers, such as triple negative and advanced estrogen receptor-positive breast cancers.
What’s next: He and his colleagues will study how hormone receptors for estrogen, testosterone, and vitamin D work together to affect DNA structure and promote cancer stem cell activity.
While DNA mutations can lead to the development of cancer, other non-genetic changes to DNA, called epigenetic modifications, control how genes are turned on or off and can also lead to cancer. Recent work by Dr. Ince’s team identified a novel regulator of epigenetic modification that leads to an increase in the expression of genes that regulate cancer stem cell growth. The process involves the activity of three hormones that are uniquely expressed together in breast cells. He is now conducting tests to determine whether targeting these hormone receptors in combination could effectively kill cancer stem cells.
Full Research Summary
Research area: Identifying new strategies to target cancer stem cells
Impact: Breast cancer stem cells constitute a minor component of the tumor cell mass but are believed to be responsible for aggressive tumor characteristics, such as resistance to cancer drugs and metastasis–the spreading of the cancer beyond the breast. Dr. Ince’s BCRF research is focused on finding ways to specifically target cancer stem cells. Work in his lab identified estrogen, testosterone and Vitamin D receptors as key players in a process that promotes cancer stem cell development and survival. While all three receptors are found in different tissues, they are uniquely expressed at the same time in breast cells, making a combination hormone approach a promising, non-chemotherapeutic approach to treatment of aggressive breast cancers.
Current research: Dr. Ince’s team is studying the effect of hormones, particularly estrogen, testosterone and Vitamin D in regulation of DNA epigenetic modifications that promote cancer stem cell survival and aggressive cancers.
What they’ve learned so far: They discovered that vitamin-D, testosterone and estrogen hormones work synergistically to control cancer stem cells by changing the structure of DNA.
What’s next: In the next year, they will continue to study the mechanism of this effect.
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. In 2010, he was recruited to the Braman Family Breast Cancer Institute at the University of Miami Miller School of 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.