Abstract 627: Establishment and characterization of a panel of cell-based and patient-derived chordoma tumor models

Abstract Background: Chordoma is a rare cancer (0.08 per 100k/yr) that originates from the notochord and develops in the skull and spine. Treatment options for chordoma include resection and local radiation therapy; however, recurrence rates following treatment are high and the majority of patients ultimately succumb to the disease. Currently there are no approved chemotherapy options for chordoma, and effective treatment options for patients with recurrent or advanced disease are limited. Recent molecular analyses of chordoma have revealed multiple tractable therapeutic targets, providing rationale for new systemic therapies. However, lack of relevant, validated chordoma models has limited preclinical evaluation. To address this need, the Chordoma Foundation and START have collaborated to establish, bank and characterize chordoma tumor models derived from patient samples and established cell lines. Methods: Chordoma patients undergoing resection or biopsy procedures are identified and consented by the Chordoma Foundation under an IRB-approved protocol; tissue is shipped to START and implanted into immune-deficient mice for patient-derived xenograft (PDX) model establishment and banking. Similarly, models from immortalized chordoma cell lines have been established and banked, along with established PDX chordoma models from START or collaborators. Banked PDX models are anonymously linked to available patient clinical information. All chordoma models are subjected to immunohistochemistry (IHC) to confirm histology and presence of brachyury, a protein highly expressed in chordoma tumors. Following validation, models are used at START for drug sensitivity studies and available to investigators for characterization studies. Results: To date, clinical samples from five chordoma patients have been implanted and two PDX models designated CF322 and CF345 have been established. In addition, xenograft models from the UCH-1 and UCH-2 chordoma cell lines have been established at START. PDX models previously developed at START (ST087) and UCSF (SF8894) have also been validated and banked. Drug sensitivity studies have been initiated these two and the U-CH1 models evaluating agents selected and prioritized through a peer review process established by the Chordoma Foundation. Nominations for additional test agents from academic and industry collaborators are reviewed on a rolling basis and evaluation of selected therapies is funded by the Chordoma Foundation. Conclusion: We have established a collaboration to create, bank and characterize a panel of preclinical chordoma tumor models originating from patient samples and established cell lines. To date we have generated three chordoma models available for drug sensitivity studies. This panel of models is intended to serve as a shared resource to the chordoma research community to enable more rapid preclinical evaluation of therapeutic hypotheses. Citation Format: Michael J. Wick, Melissa Rundle, Lizette Gamez, Armando Diaz, Josh Sommer, Patricia Cogswell, Byron Hann, Joanna Phillips, Kyriakos P. Papadopoulos. Establishment and characterization of a panel of cell-based and patient-derived chordoma tumor models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 627.