Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

Shigeru Kawabata, M. Christine Hollander, Jeeva P. Munasinghe, Lauren R. Brinster, José R. Mercado-Matos, Jie Li, Lucia Regales, William Pao, Pasi A. Jänne, Kwok Kin Wong, John A. Butman, Russell R. Lonser, Marlan R. Hansen, Richard K. Gurgel, Alexander O. Vortmeyer, Phillip A. Dennis

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms.

Original languageEnglish (US)
Pages (from-to)11357-11368
Number of pages12
JournalOncotarget
Volume6
Issue number13
DOIs
StatePublished - 2015

Keywords

  • EGFR
  • EGFR-targeted therapy
  • Ear tumorigenesis
  • Mouse model of adenomatous ear tumor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Kawabata, S., Christine Hollander, M., Munasinghe, J. P., Brinster, L. R., Mercado-Matos, J. R., Li, J., Regales, L., Pao, W., Jänne, P. A., Wong, K. K., Butman, J. A., Lonser, R. R., Hansen, M. R., Gurgel, R. K., Vortmeyer, A. O., & Dennis, P. A. (2015). Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone. Oncotarget, 6(13), 11357-11368. https://doi.org/10.18632/oncotarget.3605