Abstract 360: Erlotinib inhibits growth of a patient derived chordoma tumor xenograft.

Abstract

Abstract Chordomas are rare primary bone tumors that occur along the neuraxis. Current treatment includes surgical resection and often postoperative radiotherapy. Despite treatment, local recurrence occurs in the majority of patients and metastasis is frequent. Treatment options for patients with recurrence is limited and, notably, there are no FDA approved chemotherapeutic agents. Median survival is approximately 7 years. The lack of treatment options is in part due to the paucity of preclinical model systems for this tumor. We have previously established a serially transplantable animal model directly from human chordoma tissue. Further analysis of this patient derived xenograft demonstrates that subsequent passages continue to resemble the original patient tumor histologically and immunohistochemically and maintain nuclear expression of brachyury, a marker for chordoma. Genome wide variation between the patient's tumor and xenografts continues to be more than 99% concordant. To further characterize this model, a receptor tyrosine kinase screen of more than 70 kinases was evaluated and epidermal growth factor receptor (EGFR) was found to be the most activated kinase. In vitro studies demonstrate that EGFR inhibitors, such as erlotinib and gefitinib, inhibit growth of a validated human chordoma cell line, U-CH1. In vivo studies demonstrate that erlotinib significantly inhibits growth of this patient derived chordoma xenograft. Evaluation of tumors post-treatment reveals that erlotinib reduces tumor proliferation and phosphorylation of EGFR. Taken together, these findings demonstrate targeting EGFR can inhibit chordoma growth in vivo and support further clinical evaluation of EGFR inhibitors in the treatment of this disease. Citation Format: I-Mei Siu, Peter C. Burger, Qi Zhao, Jacob Ruzevick, Nick Connis, Christine L. Hann, Gary L. Gallia. Erlotinib inhibits growth of a patient derived chordoma tumor xenograft. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 360. doi:10.1158/1538-7445.AM2013-360