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Tumor Biology of Vestibular Schwannoma: A Review of Experimental Data on the Determinants of Tumor Genesis and Growth Characteristics

de Vries, Maurits*†; van der Mey, Andel G. L.; Hogendoorn, Pancras C. W.*

doi: 10.1097/MAO.0000000000000788
Review Articles

Objective Provide an overview of the literature on vestibular schwannoma biology with special attention to tumor behavior and targeted therapy.

Background Vestibular schwannomas are benign tumors originating from the eighth cranial nerve and arise due to inactivation of the NF2 gene and its product merlin. Unraveling the biology of these tumors helps to clarify their growth pattern and is essential in identifying therapeutic targets.

Methods PubMed search for English-language articles on vestibular schwannoma biology from 1994 to 2014.

Results Activation of merlin and its role in cell signaling seem as key aspects of vestibular schwannoma biology. Merlin is regulated by proteins such as CD44, Rac, and myosin phosphatase-targeting subunit 1. The tumor-suppressive functions of merlin are related to receptor tyrosine kinases, such as the platelet-derived growth factor receptor and vascular endothelial growth factor receptor. Merlin mediates the Hippo pathway and acts within the nucleus by binding E3 ubiquiting ligase CRL4DCAF1. Angiogenesis is an important mechanism responsible for the progression of these tumors and is affected by processes such as hypoxia and inflammation. Inhibiting angiogenesis by targeting vascular endothelial growth factor receptor seems to be the most successful pharmacologic strategy, but additional therapeutic options are emerging.

Conclusion Over the years, the knowledge on vestibular schwannoma biology has significantly increased. Future research should focus on identifying new therapeutic targets by investigating vestibular schwannoma (epi)genetics, merlin function, and tumor behavior. Besides identifying novel targets, testing new combinations of existing treatment strategies can further improve vestibular schwannoma therapy.

Supplemental digital content is available in the text.

Departments of *Pathology and †Otolaryngology, Leiden University Medical Center, Leiden, The Netherlands

Address correspondence and reprint requests to Maurits de Vries, M.D., Department of Otolaryngology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; E-mail:

Conflicts of interest and source of funding: This study was supported by a departmental grant; the authors declare no conflict of interest.

Supplemental digital content is available in the text.

Copyright © 2015 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company