Erlotinib inhibits growth of a patient-derived chordoma xenograft

I. Mei Siu, Jacob Ruzevick, Qi Zhao, Nick Connis, Yuchen Jiao, Chetan Bettegowda, Xuewei Xia, Peter C. Burger, Christine Hann, Gary L Gallia

Research output: Contribution to journalArticle

Abstract

Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.

Original languageEnglish (US)
Article numbere78895
JournalPLoS One
Volume8
Issue number11
DOIs
StatePublished - Nov 15 2013

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Chordoma
Epidermal Growth Factor Receptor
Heterografts
Tumors
Growth
neoplasms
Neoplasms
Phosphorylation
Radiotherapy
Therapeutics
therapeutics
Surgery
radiotherapy
Bone
Demonstrations
Genes
in vitro studies
Chemical activation
Cells
genotyping

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Erlotinib inhibits growth of a patient-derived chordoma xenograft. / Siu, I. Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C.; Hann, Christine; Gallia, Gary L.

In: PLoS One, Vol. 8, No. 11, e78895, 15.11.2013.

Research output: Contribution to journalArticle

Siu, IM, Ruzevick, J, Zhao, Q, Connis, N, Jiao, Y, Bettegowda, C, Xia, X, Burger, PC, Hann, C & Gallia, GL 2013, 'Erlotinib inhibits growth of a patient-derived chordoma xenograft', PLoS One, vol. 8, no. 11, e78895. https://doi.org/10.1371/journal.pone.0078895
Siu, I. Mei ; Ruzevick, Jacob ; Zhao, Qi ; Connis, Nick ; Jiao, Yuchen ; Bettegowda, Chetan ; Xia, Xuewei ; Burger, Peter C. ; Hann, Christine ; Gallia, Gary L. / Erlotinib inhibits growth of a patient-derived chordoma xenograft. In: PLoS One. 2013 ; Vol. 8, No. 11.
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