Department of Neurological Surgery, University of California, Los Angeles, CA 90095-1761, USA.
J Neurosurg. 2011 Nov;115(5):906-14. doi: 10.3171/2011.6.JNS11131. Epub 2011 Jul 29.
Vestibular schwannomas are histopathologically benign tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product merlin. Merlin acts as a tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of vestibular schwannomas as well as the development of novel therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of vestibular schwannomas as well as the development of modern treatments for vestibular schwannoma. For instance, merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently, merlin was also shown to interact in the nucleus with E3 ubiquitin ligase CRL4(DCAF1). A greater understanding of the molecular mechanisms behind vestibular schwannoma tumorigenesis has begun to yield novel therapies. Some authors have shown that Avastin induces regression of progressive schwannomas by over 40% and improves hearing. An inhibitor of VEGF synthesis, PTC299, is currently in Phase II trials as a potential agent to treat vestibular schwannoma. Furthermore, in vitro studies have shown that trastuzumab (an ERBB2 inhibitor) reduces vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing tumor burden, tumor volume, hearing loss, and cranial nerve deficits seen in vestibular schwannomas.
前庭神经鞘瘤是一种组织病理学良性肿瘤，起源于第八颅神经前庭支的施万细胞鞘，与 NF2 基因及其产物 Merlin 有关。 Merlin 作为一种肿瘤抑制因子和接触抑制的介质。因此，NF2 基因的缺失都会导致前庭神经鞘瘤的发展。最近，我们对前庭神经鞘瘤的分子生物学以及其治疗的新疗法有了重大进展。本文作者全面回顾了前庭神经鞘瘤的分子生物学和特征的最新进展以及现代治疗前庭神经鞘瘤的方法。例如， Merlin 与许多受体有关，包括 CD44 受体、EGFR 以及信号通路，如 Ras/raf 通路和经典的 Wnt 通路。最近， Merlin 还被证明在核内与 E3 泛素连接酶 CRL4（DCAF1）相互作用。对前庭神经鞘瘤肿瘤发生背后的分子机制的深入了解已经开始产生新的疗法。一些作者表明，Avastin 通过超过 40%的比例诱导进行性神经鞘瘤的消退，并改善听力。VEGF 合成抑制剂 PTC299 目前正在进行 II 期临床试验，作为治疗前庭神经鞘瘤的潜在药物。此外，体外研究表明曲妥珠单抗（一种 ERBB2 抑制剂）可降低前庭神经鞘瘤细胞的增殖。通过进一步的研究，通过减少肿瘤负担、肿瘤体积、听力损失和前庭神经鞘瘤的颅神经缺陷，有可能显著降低发病率和死亡率。
