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    Newswise  (New York  January 30, 2015) Two existing cancer    drugs turn on a gene that tells tumor cells to remain inactive,    according to a study led by researchers at the Icahn School of    Medicine at Mount Sinai and published today in Nature    Communications.  
    Researchers discovered that the gene NR2F1, when switched on,    programs tumor cells to stay dormant. When the gene is switched    off, tumor cells divide and multiply as part of abnormal    growth, potentially allowing dormant cells to grow into tumors    throughout the body (metastasis). Combining the anticancer    drugs azacytidine and retinoic acid significantly increased the    amount of active NR2F1 in tumor cells. These patterns were    found in mouse models of several cancers, and confirmed in    prostate cancer cells from human patients.  
    Results suggest that NR2F1 is a master regulator of tumor    cell growth, influencing several genes that determine whether    cells remain inactive, or quiescent in medical terms. According    to the study, NR2F1 exerts control over long lasting programs    in stem cells in the human embryo, where it directs cells to    stop growing and become specialized cells (neurons) for life.    This function suggests that NR2F1 may exert a long-lasting    effect on tumor cells, keeping them dormant after they have    broken off from an original tumor.  
    Our results explain why some tumor cells scattered through the    body are committed to remaining harmless for years, while    others cause active disease, said Julio A. Aguirre-Ghiso, PhD,    Professor of Medicine, Hematology and Medical Oncology, and    Otolaryngology at the Icahn School of Medicine. In finding    this master switch we found a way to analyze tumor cells before    treatment to determine the risk of a cancer recurrence or    metastasis.  
    Azacytidine and retinoic acid, the latter a form of vitamin A,    prevented tumor cells from rapidly multiplying, restored normal    cell function, and activated several tumor suppressor genes    that are often turned off in tumors, said study co-leader    Maria Soledad Sosa, PhD, a postdoctoral fellow in Hematology at    the Icahn School of Medicine. We now have strong evidence that    combining these well-known drugs may have a profound,    long-lasting therapeutic effect.  
    The current study builds on the research teams earlier finding    that lowering amounts of tumor suppressor genes TGF2 and p38    awakened dormant tumor cells, fueling metastatic tumor growth.    Azacytidine and retinoic acid restored TGF2 expression and p38    activation to drive tumor cell dormancy.  
    This study was supported by grants from the Samuel Waxman    Cancer Research Foundation, National Cancer Institute, National    Institute of Environmental Health Sciences, New York State Stem    Cell Science program, JJR Foundation and Hirschl/Weill-Caulier    Trust, Department of Defense and Janssen Research and    Development LLC.  
    About the Mount Sinai Health System    The Mount Sinai Health System is an integrated health system    committed to providing distinguished care, conducting    transformative research, and advancing biomedical education.    Structured around seven member hospital campuses and a single    medical school, the Health System has an extensive ambulatory    network and a range of inpatient and outpatient servicesfrom    community-based facilities to tertiary and quaternary care.  
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Master Switch Found to Stop Tumor Cell Growth by Inducing Dormancy