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

doi:10.18632/oncotarget.3605

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

Journal article

Open access

Peer reviewed

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, …

Oncotarget, Vol.6(13), pp.11357-11368

05/10/2015

DOI: 10.18632/oncotarget.3605

PMCID: PMC4484461

PMID: 26027747

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https://doi.org/10.18632/oncotarget.3605View

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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.

Drug Design

Magnetic Resonance Imaging

Phenotype

Mutation

Skull Neoplasms - drug therapy

Temporal Bone - metabolism

Receptor, Epidermal Growth Factor - genetics

Adenocarcinoma - pathology

Humans

Male

Molecular Targeted Therapy

Motor Activity

Uteroglobin - metabolism

X-Ray Microtomography

Adenoma - metabolism

Behavior, Animal

Neoplasms, Experimental - pathology

Receptor, Epidermal Growth Factor - metabolism

Adenocarcinoma - metabolism

Ear Neoplasms - genetics

Ear, Middle - metabolism

Skull Neoplasms - metabolism

Adenoma - drug therapy

Neoplasms, Experimental - genetics

Skull Neoplasms - pathology

Female

Antineoplastic Agents - pharmacology

Ear, Middle - pathology

Ear, Middle - drug effects

Promoter Regions, Genetic

Ear Neoplasms - pathology

Ear Neoplasms - drug therapy

Temporal Bone - drug effects

Uteroglobin - genetics

Genotype

Mice, Transgenic

Ear Neoplasms - metabolism

Temporal Bone - pathology

Animals

Signal Transduction - drug effects

Adenoma - pathology

Pulmonary Surfactant-Associated Protein C - genetics

Receptor, Epidermal Growth Factor - antagonists & inhibitors

Neoplasms, Experimental - metabolism

Neoplasms, Experimental - drug therapy

Details

Title: Subtitle: Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone
Creators: Shigeru Kawabata - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
M Christine Hollander - Present address: Laboratory of Cancer Biology and Genetics, CCR, NCI, Bethesda, MD, USA
Jeeva P Munasinghe - Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD, USA
Lauren R Brinster - Division of Veterinary Resources, NIH, Bethesda, MD, USA
José R Mercado-Matos - Medical Oncology Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
Jie Li - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
Lucia Regales - Memorial Sloan-Kettering Cancer Center, New York, USA
William Pao - Division of Hematology-Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
Pasi A Jänne - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Kwok-Kin Wong - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
John A Butman - Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA
Russell R Lonser - Surgical Neurology Branch, NINDS, NIH, Bethesda, MD, USA
Marlan R Hansen - Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Richard K Gurgel - Division of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, UT, USA
Alexander O Vortmeyer - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
Phillip A Dennis - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.6(13), pp.11357-11368
DOI: 10.18632/oncotarget.3605
PMID: 26027747
PMCID: PMC4484461
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: United States
Grant note: R01 CA135257 / NCI NIH HHS R01CA135257 / NCI NIH HHS R01 DC009801 / NIDCD NIH HHS P01CA129243 / NCI NIH HHS R01CA121210 / NCI NIH HHS P01 CA129243 / NCI NIH HHS R01 CA121210 / NCI NIH HHS
Language: English
Date published: 05/10/2015
Academic Unit: Molecular Physiology and Biophysics; Neurosurgery; Otolaryngology
Record Identifier: 9984006353002771

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