Abstract LB-110: Establishment of a chordoma xenograft and in vivo testing of compounds identified by high-throughput screening

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 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. We have established a chordoma xenograft growing in NOD/SCID/IL-2R gamma-null mice. The histology of the xenograft is consistent with a dedifferentiated chordoma. The xenograft expresses the chordoma marker T brachyury, which is aberrantly localized in the cytoplasm. SNP array shows loss of heterozygosity at the p16 locus, and gene expression profiling shows high expression of numerous cancer-related genes, such as ROS1 and CPA4 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. Compared with mice treated with vehicle alone, both drugs showed a dramatic inhibition of tumor growth. In conclusion, we have established a xenograft model of dedifferentiated chordoma. High-throughput screening of compounds identified compounds that show activity against chordoma. In vivo testing of two identified compounds showed a dramatic reduction of tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-110. doi:1538-7445.AM2012-LB-110