神经鞘瘤
梅林(蛋白质)
医学
癌症研究
前庭系统
受体酪氨酸激酶
表皮生长因子受体
生长因子受体
血管生成
血管内皮生长因子
病理
生物
神经科学
受体
内科学
癌症
血管内皮生长因子受体
抑制器
作者
Margreet de Vries,Andel G. L. van der Mey,Pancras C.W. Hogendoorn
出处
期刊:Otology & Neurotology
[Ovid Technologies (Wolters Kluwer)]
日期:2015-08-01
卷期号:36 (7): 1128-1136
被引量:35
标识
DOI:10.1097/mao.0000000000000788
摘要
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.
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