Karmanos Cancer Institute scientists identify potential new target for breast cancer therapy

ORLANDO – The American Society of Clinical Oncology (ASCO) has selected new breast cancer research conducted at the Barbara Ann Karmanos Cancer Institute in Detroit for posting on ASCO’s Web site. Karmanos’ potentially ground-breaking findings identify a promising new therapeutic target for aggressive hormone receptor negative breast cancer tumors. The research appears at www.ASCO.org and http://www.jco.org and is entitled “Enhancer of Zeste Homologue 2 (EZH-2) expression in breast cancer: a novel marker and potential target.” Karmanos scientists tested 84 cases of hormone receptor negative human breast carcinomas and discovered that the protein EZH-2 was expressed in 74 percent of those cases. Hormone receptor negative breast carcinoma is considered an aggressive cancer and one that is hard to treat. The finding suggests that EZH-2 could be an important therapeutic target in this patient population. “We were interested in looking at a new target,” said Zeina Nahleh, M.D., co-director of the Breast Oncology Multidisciplinary Team at Karmanos Cancer Institute and assistant professor of medicine in hematology and oncology at Wayne State University School of Medicine. “We wanted to see how much expression of the protein was present. We were surprised that 74 percent of tumors expressed that EZH-2 protein.” Sixty-one samples that researchers used were triple negative breast cancer cases and 23 cases were HER-2/neu positive. Scientists found that the increased expression of EZH-2 meant an increase in tumor size and an increase in lymph node metastasis. Dr. Nahleh said that increased identification of proteins in these aggressive forms of breast cancer is needed to develop better treatments. The discovery of the high rate of EZH-2 protein expression in breast cancer cases opens up a new avenue in doing just that. “We are extremely excited about this discovery,” she said. “This is amazing work. In the future, this could be a target for therapy.” The identification of EZH-2 represents just the first step in the mission to find more proteins that cause deadly breast cancer tumors and assess them for possible therapeutic targets. There is much work ahead, according to Dr. Nahleh. “The ground-breaking work will come if we can identify a specific method to target this EZH-2 protein and show that this approach would lead to meaningful clinical results,” she said. “We have to go back and look at survival rates. We have to consider years of follow-up work and we have to look at other associated factors. “This will hopefully lead to new targeted therapy strategies based on our new understanding of the biology of cancer.” Fellow investigators include Sudeshna Bandyopadhyay, M.D., of Wayne State University School of Medicine; Rouba Ali Fehmi, M.D., of the Karmanos Cancer Institute and Wayne State University School of Medicine; Haitham Arabi, M.D., resident of the Wayne State University School of Medicine’s Department of Pathology ; Wael Sakr, M.D., of the Karmanos Cancer Institute and Wayne State University School of Medicine; Adnan Munkarah, M.D., of the Henry Ford Health System in Detroit; and Michael Kruger, statistical analyst with Wayne State University School of Medicine’s Department of Obstetrics and Gynecology. Dr. Nahleh noted that the discovery of a potential therapeutic target wouldn’t be possible without the laboratory and clinical breast cancer research at Karmanos and its collaborative partnerships. “I think this discovery highlights the importance of multidisciplinary work in oncology between clinical and scientific researchers,” she said. “This is what Karmanos is all about.”

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1. Karmanos Cancer Institute scientists identify potential new target for breast cancer therapy