de Vries Maurits, van der Mey Andel G L, Hogendoorn Pancras C W
Departments of *Pathology and †Otolaryngology, Leiden University Medical Center, Leiden, The Netherlands.
Otol Neurotol. 2015 Aug;36(7):1128-36. doi: 10.1097/MAO.0000000000000788.
Provide an overview of the literature on vestibular schwannoma biology with special attention to tumor behavior and targeted therapy.
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.
PubMed search for English-language articles on vestibular schwannoma biology from 1994 to 2014.
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 CRL4. 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.
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.
概述关于前庭神经鞘瘤生物学的文献，特别关注肿瘤行为和靶向治疗。
前庭神经鞘瘤是起源于第八颅神经的良性肿瘤，由NF2基因及其产物默林蛋白失活引起。阐明这些肿瘤的生物学特性有助于明确其生长模式，对于确定治疗靶点至关重要。
在PubMed上检索1994年至2014年关于前庭神经鞘瘤生物学的英文文章。
默林蛋白的激活及其在细胞信号传导中的作用似乎是前庭神经鞘瘤生物学的关键方面。默林受CD44、Rac和肌球蛋白磷酸酶靶向亚基1等蛋白质调节。默林的肿瘤抑制功能与受体酪氨酸激酶有关，如血小板衍生生长因子受体和血管内皮生长因子受体。默林介导Hippo信号通路，并通过结合E3泛素连接酶CRL4在细胞核内发挥作用。血管生成是这些肿瘤进展的重要机制，受缺氧和炎症等过程影响。通过靶向血管内皮生长因子受体抑制血管生成似乎是最成功的药物策略，但新的治疗选择也不断涌现。
多年来，关于前庭神经鞘瘤生物学的知识有了显著增加。未来的研究应集中于通过研究前庭神经鞘瘤的（表观）遗传学、默林蛋白功能和肿瘤行为来确定新的治疗靶点。除了确定新靶点外，测试现有治疗策略的新组合可进一步改善前庭神经鞘瘤的治疗。
