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

Abstract

Abstract

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 till 2014. Results: activation of merlin and its role in cell signaling seem key aspects of vestibular schwannoma biology. Merlin is regulated by proteins like CD44, Rac and myosin phosphatase targeting subunit 1 (MYPT1). The tumor suppressive functions of merlin are related to receptor tyrosine kinases, such as the platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGF). 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 like hypoxia and inflammation. Inhibiting angiogenesis by targeting VEGF seems to be the most successful pharmacological 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.