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 Vortmeyer, Phillip A. Dennis

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 - Jan 1 2015
Externally publishedYes

Fingerprint

Temporal Bone
Middle Ear
Epidermal Growth Factor Receptor
Neoplasms
Ear
Ear Neoplasms
Lung Neoplasms
Therapeutics
Head
Magnetic Resonance Imaging
Lung

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Kawabata, S., Christine Hollander, M., Munasinghe, J. P., Brinster, L. R., Mercado-Matos, J. R., Li, J., ... 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

Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone. / Kawabata, Shigeru; Christine Hollander, M.; Munasinghe, Jeeva P.; Brinster, Lauren R.; Mercado-Matos, José R.; Li, Jie; Regales, Lucia; Pao, William; Jänne, Pasi A.; Wong, Kwok Kin; Butman, John A.; Lonser, Russell R.; Hansen, Marlan R.; Gurgel, Richard K.; Vortmeyer, Alexander; Dennis, Phillip A.

In: Oncotarget, Vol. 6, No. 13, 01.01.2015, p. 11357-11368.

Research output: Contribution to journalArticle

Kawabata, S, Christine Hollander, M, Munasinghe, JP, Brinster, LR, Mercado-Matos, JR, Li, J, Regales, L, Pao, W, Jänne, PA, Wong, KK, Butman, JA, Lonser, RR, Hansen, MR, Gurgel, RK, Vortmeyer, A & Dennis, PA 2015, 'Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone', Oncotarget, vol. 6, no. 13, pp. 11357-11368. https://doi.org/10.18632/oncotarget.3605
Kawabata S, Christine Hollander M, Munasinghe JP, Brinster LR, Mercado-Matos JR, Li J et al. Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone. Oncotarget. 2015 Jan 1;6(13):11357-11368. https://doi.org/10.18632/oncotarget.3605
Kawabata, Shigeru ; Christine Hollander, M. ; Munasinghe, Jeeva P. ; Brinster, Lauren R. ; Mercado-Matos, José R. ; Li, Jie ; Regales, Lucia ; Pao, William ; Jänne, Pasi A. ; Wong, Kwok Kin ; Butman, John A. ; Lonser, Russell R. ; Hansen, Marlan R. ; Gurgel, Richard K. ; Vortmeyer, Alexander ; Dennis, Phillip A. / Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone. In: Oncotarget. 2015 ; Vol. 6, No. 13. pp. 11357-11368.
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