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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
Seeking novel approaches for the treatment of breast cancer by targeting cancer stem cells.
Laboratory studies are conducted to test a drug cocktail to target multiple regulators of cancer stem cell growth.
If successful, these studies could reveal a non-chemotherapeutic breast cancer stem cell targeted therapy.
Many environmental and lifestyle factors including diet, exercise, and hormones influence development of breast cancer. While lifestyle or hormonal factors do not cause genetic mutations outright, they may affect gene regulation in a non-genetic way.
Dr. Ince's laboratory discovered that estrogen receptors, androgen receptors, and vitamin D receptors work with DNA packaging protein in a so called "epigenetic program" (attaching reversible chemical modification of the DNA) to regulate cancer stem cells.
The group previously reported that patients with breast cancers that express estrogen receptors, androgen receptors, and vitamin D receptors are seven-fold more likely to survive compared to patients with breast cancer that expresses none of these receptors.
In the upcoming year, Dr. Ince and his team will target breast cancer using combinations of drugs against estrogen receptors, androgen receptors, and vitamin D receptors, with drugs that reverse epigenetic modification.
The goal of Dr. Ince's research is to translate these discoveries to the clinic and develop new strategies for treatment, because unlike genetic mutations that are permanent, epigenetic changes are reversible.
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.