308 hibit tumor growth and metastasis in an orthotopic mouse model of human ATC harboring B-RafV600E. Additionally, our in vitro model using primary human NT cells (heterozy- gous wt B-Raf/B-RafV600E) recapitulates the genetic status of this mutation in human thyroid cancer; it is the first trans- lational demonstration to show that PLX4720 is effective in a B-RafV600E heterozygous model. Our results suggest that PLX4720 might be an effective therapy in clinical trials for the treatment of patients with B-RafV600E-positive thyroid cancers that are refractory to conventional therapy. ACKNOWLEDGMENTS Carmelo Nucera was funded through A. Gemelli Medical School (Catholic University, Rome) grants and Italian Min- istry of Education (MIUR) (Italy) grants. Richard A. Hodin was funded by NIH T32 #5T32 DK007754-10. Other fund- ing included research funds to Sareh Parangi, Jack Lawler, and Richard A. Hodin from NIH DK050623, DK047186, CA130895, CA130895, ATA, and the Polsky Fund. 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PLX4720 and Preclinical Thyroid Cancer Models thank Dr. Yutaka Kawami (Keio University, Tokyo, Japan) for providing HIV-U6 vectors, Dr. Shou-Ching Shih for help with the RT-PCR, and Mark Duquette for technical assistance, as well as the Center for Cancer Genome Discovery (Dana Farber Cancer Institute) and the Center for Systems Biology Mouse Imaging Program (Massachusetts General Hospital). We thank Drs. Efisio Puxeddu and Sonia Moretti (University of Perugia) for RET/PTC-1 analysis of TPC-1 cells. Carmelo Nucera and Matthew A. Nehs contributed equally to this work. AUTHOR CONTRIBUTIONS Conception/Design: Carmelo Nucera, Matthew A. Nehs, Sareh Parangi Provision of study material or patients: Carmelo Nucera, Matthew A. Nehs, Peter M. Sadow, Paul S. Lin, Gideon E. Bollag, Jack Lawler, Sareh Parangi Collection and/or assembly of data: Carmelo Nucera, Matthew A. Nehs, Sushruta S. Nagarkatti, Peter M. Sadow, Michal Mekel, Andrew H. 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