Yoo, ByungheeKavishwar, AmolWang, PingRoss, AlanaPantazopoulos, PamelaDudley, MichaelMoore, AnnaMedarova, Zdravka2017-04-062017Yoo, Byunghee, Amol Kavishwar, Ping Wang, Alana Ross, Pamela Pantazopoulos, Michael Dudley, Anna Moore, and Zdravka Medarova. 2017. “Therapy targeted to the metastatic niche is effective in a model of stage IV breast cancer.” Scientific Reports 7 (1): 45060. doi:10.1038/srep45060. http://dx.doi.org/10.1038/srep45060.http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071972Treatment of stage IV metastatic breast cancer patients is limited to palliative options and represents an unmet clinical need. Here, we demonstrate that pharmacological inhibition of miRNA-10b - a master regulator of metastatic cell viability – leads to elimination of distant metastases in a mouse model of metastatic breast cancer. This was achieved using the miRNA-10b inhibitory nanodrug, MN-anti-miR10b, which consists of magnetic nanoparticles, conjugated to LNA-based miR-10b antagomirs. Intravenous injection of MN-anti-miR10b into mice bearing lung, bone, and brain metastases from breast cancer resulted in selective accumulation of the nanodrug in metastatic tumor cells. Weekly treatments of mice with MN-anti-miR-10b and low-dose doxorubicin resulted in complete regression of pre-existing distant metastases in 65% of the animals and a significant reduction in cancer mortality. These observations were supported by dramatic reduction in proliferation and increase in apoptosis in metastatic sites. On a molecular level, we observed a significant increase in the expression of HOXD10, which is a known target of miRNA-10b. These results represent first steps into the uncharted territory of therapy targeted to the metastatic niche.en-USJournal Article2017-04-0610.1038/srep45060