Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model

Jinu Abraham, Laura D. Nelon, Courtney B. Kubicek, Aoife Kilcoyne, Sheila T. Hampton, Lee Ann Zarzabal, Francis J. Giles, Joel E Michalek, Brian P. Rubin, Charles Keller

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Rhabdomyosarcoma is an aggressive childhood malignancy, accounting for more than 50 of all soft-tissue sarcomas in children. Even with extensive therapy, the survival rate among alveolar rhabdomyosarcoma patients with advanced disease is only 20. The receptor tyrosine kinase Epidermal Growth Factor Receptor (EGFR) has been found to be expressed and activated in human rhabdomyosarcomas. In this study we have used a genetically engineered mouse model for alveolar rhabdomyosarcoma (ARMS) which faithfully recapitulates the human disease by activating the pathognomic Pax3:Fkhr fusion gene and inactivating p53 in the maturing myoblasts. We have demonstrated that tumors from our mouse model of alveolar rhabdomyosarcoma express EGFR at both the mRNA and protein levels. We then tested the EGFR inhibitor, Erlotinib, for its efficacy in this mouse model of alveolar rhabdomyosarcoma. Surprisingly, Erlotinib had no effect on tumor progression, yet mice treated with Erlotinib showed 10-20 loss of body weight. These results suggest that EGFR might not be an a priori monotherapy target in alveolar rhabdomyosarcoma.

Original languageEnglish (US)
Article number130484
JournalSarcoma
Volume2011
DOIs
StatePublished - 2011

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Alveolar Rhabdomyosarcoma
Epidermal Growth Factor Receptor
Rhabdomyosarcoma
Neoplasms
Myoblasts
Gene Fusion
p53 Genes
Sarcoma
Survival Rate
Body Weight
Erlotinib Hydrochloride
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Abraham, J., Nelon, L. D., Kubicek, C. B., Kilcoyne, A., Hampton, S. T., Zarzabal, L. A., ... Keller, C. (2011). Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model. Sarcoma, 2011, [130484]. https://doi.org/10.1155/2011/130484

Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model. / Abraham, Jinu; Nelon, Laura D.; Kubicek, Courtney B.; Kilcoyne, Aoife; Hampton, Sheila T.; Zarzabal, Lee Ann; Giles, Francis J.; Michalek, Joel E; Rubin, Brian P.; Keller, Charles.

In: Sarcoma, Vol. 2011, 130484, 2011.

Research output: Contribution to journalArticle

Abraham, J, Nelon, LD, Kubicek, CB, Kilcoyne, A, Hampton, ST, Zarzabal, LA, Giles, FJ, Michalek, JE, Rubin, BP & Keller, C 2011, 'Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model', Sarcoma, vol. 2011, 130484. https://doi.org/10.1155/2011/130484
Abraham J, Nelon LD, Kubicek CB, Kilcoyne A, Hampton ST, Zarzabal LA et al. Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model. Sarcoma. 2011;2011. 130484. https://doi.org/10.1155/2011/130484
Abraham, Jinu ; Nelon, Laura D. ; Kubicek, Courtney B. ; Kilcoyne, Aoife ; Hampton, Sheila T. ; Zarzabal, Lee Ann ; Giles, Francis J. ; Michalek, Joel E ; Rubin, Brian P. ; Keller, Charles. / Preclinical testing of Erlotinib in a transgenic alveolar rhabdomyosarcoma mouse model. In: Sarcoma. 2011 ; Vol. 2011.
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