Abstract | BACKGROUND: Pharmacologic agents targeted against the ErbB family, or the intracellular pathways that mediate their effects, could slow clinical progression of vestibular schwannoma (VS) in patients where other modalities carry a high risk-to-benefit ratio. OBJECTIVE: Determine the identity of the predominant ErbB dimer partners in VS tumors and assess the effects of targeted inhibition of the ErbB molecules on VS growth and proliferation, as well as apoptosis. SETTING: Academic tertiary referral center. METHODS: RESULTS: Activated ErbB family receptor heterodimers in VS contain predominantly epidermal growth factor receptor (EGFR) and ErbB2. A robust, dose-dependent inhibition of VS growth and proliferation with the dual EGFR/ErbB2 inhibitor, lapatinib, was demonstrated. Lapatinib also inhibited EGF-induced VS proliferation. The selective ErbB2 inhibitor, AG825, inhibited growth to a lesser extent. HEI193 demonstrated apoptosis after lapatinib treatment. CONCLUSION: Dual EGFR and ErbB2 inhibition with lapatinib or combination therapy may provide therapeutic benefit in VS treatment, but further studies are necessary.
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Authors | Zana K Ahmad, Carrie M Brown, Roberto A Cueva, Allen F Ryan, Joni K Doherty |
Journal | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
(Otol Neurotol)
Vol. 32
Issue 5
Pg. 841-7
(Jul 2011)
ISSN: 1537-4505 [Electronic] United States |
PMID | 21659924
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Benzothiazoles
- Protein Kinase Inhibitors
- Quinazolines
- Tyrphostins
- tyrphostin AG825
- Lapatinib
- Epidermal Growth Factor
- ERBB2 protein, human
- Receptor, ErbB-2
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Topics |
- Benzothiazoles
(pharmacology)
- Cell Cycle
(drug effects)
- Cell Proliferation
(drug effects)
- Epidermal Growth Factor
(antagonists & inhibitors, metabolism)
- Humans
- Lapatinib
- Neuroma, Acoustic
(metabolism, pathology)
- Protein Kinase Inhibitors
(pharmacology)
- Quinazolines
(pharmacology)
- Receptor, ErbB-2
(antagonists & inhibitors, metabolism)
- Signal Transduction
(drug effects)
- Tumor Cells, Cultured
- Tyrphostins
(pharmacology)
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