Establishment of a chordoma xenograft and in vivo testing of compounds identified by high-throughput screening.

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10025 Background: Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. Therapy primarily consists of surgical resection and radiation. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents for chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Methods: Primary tumor from a classic sacral chordoma was obtained, immediately processed into a single cell suspension and injected in to the parasacral area of a NOD/SCID/IL-2R gamma-null mouse, and tumor grew after 3 months. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds. Two established chordoma cell lines, U-CH1 and UCH2B, were treated and cell viability measured by CellTiter-Glo assay. Cells were incubated for 48 hours with drug concentrations ranging from 0.5nM to 46uM. The screen yielded several compounds that showed activity and two were tested in the xenograft. Results: We have established a xenograft model of dedifferentiated chordoma. High-throughput screening of compounds identified compounds that show activity against chordoma cell lines. In vivo testing of two identified compounds showed a dramatic reduction of tumor growth. Conclusions: We have established a xenograft model of dedifferentiated chordoma. High-throughput screening of compounds identified compounds that show activity against chordoma cell lines. In vivo testing of two identified compounds showed a dramatic reduction of tumor growth.