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Targeting Antioxidant Enzymes May Kill Metastasizing Cancer Cells

A new study by a team of researchers from the University of Notre Dame provides an important new insight into how cancer cells are able to avoid the cell death process. The findings may suggest a chemotherapeutic approach to prevent the spread of cancers. Metastasis, the spread of cancer from one organ to other parts of the body, relies on cancer cells’ ability to evade a cell death process called anoikis, according to Dr. Zachary T. Schafer, Coleman Assistant Professor of Cancer Biology at Notre Dame. Metastasizing cancer cells are able to survive anoikis, which normally results from detachment from the extracellular matrix. However, Schafer notes that the molecular mechanisms cancer cells detached from the extracellular matrix use to survive has not been well understood. "This paper reveals that cancer cells that are detached from their normal environment, as they would be during metastasis, rely on the activity of antioxidant enzymes to facilitate their survival," Dr. Schafer said. "This class of enzymes is critical for neutralizing oxidative stress and function much like the compounds that are present in a variety of foods." The paper describes a prominent role for antioxidant enzymes in facilitating the survival of breast cancer cells after detachment from the extracellular matrix. Conversely, the researchers report, silencing antioxidant enzyme expression reduced tumor formation. "The results in this paper suggest that targeting antioxidant enzymes with novel therapeutics may selectively kill off metastasizing cancer cells," Dr. Schafer said. The paper appears in the June 15, 2013 issue of Cancer Research, which is the most frequently cited cancer journal in the world. The research team collaborated with Dr. Matthew Leevy in Notre Dame's in vivo imaging facility. Other authors of the paper include doctoral student Calli Davison, rising junior Sienna Durbin, 2011 alum Matthew Thau, graduate student Victoria Zellmer, and Sarah Chapman, Justin Diner and Connor Wathen from the Notre Dame Integrated Imaging Facility. [Press release] [Cancer Research abstract]