The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions
The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions
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DOI：
10.1007/s40265-016-0552-9
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发表时间：
2016-04-01
期刊：
影响因子：
11.5
通讯作者：
Zonnenberg, Bernard A.
中科院分区：
文献类型：
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作者：
Curatolo, Paolo;Bjornvold, Marit;Zonnenberg, Bernard A.
结节性硬化症 (TSC) 是一种由 TSC1 或 TSC2 基因突变引起的遗传性疾病。由此产生的哺乳动物雷帕霉素靶点 (mTOR) 信号通路的过度激活使 TSC 患者的多个器官中的非恶性肿瘤容易生长。此前，手术是 TSC 的主要治疗选择。然而，使用 mTOR 抑制剂（例如依维莫司和西罗莫司）的药物治疗现已成为一种替代方法。依维莫司和西罗莫司已被证明可有效治疗室管膜下巨细胞星形细胞瘤 (SEGA) 和肾血管平滑肌脂肪瘤 (AML)，目前正在评估依维莫司治疗 TSC 相关癫痫的效果。 2013 年 11 月，一组欧洲专家召开会议，讨论治疗 TSC 各种表现的当前选择和实际考虑因素。本文为 SEGA、TSC 相关癫痫和肾性 AML 的治疗提供循证建议，重点关注 mTOR 抑制剂治疗可与其他治疗方案一起考虑的情况。还回顾了有关 mTOR 抑制剂治疗的安全性考虑因素。有证据表明 mTOR 抑制剂对神经系统和非神经系统 TSC 表现有益，可能代表 TSC 的全身治疗。
Tuberous sclerosis complex (TSC) is a genetic disorder arising from mutations in the TSC1 or TSC2 genes. The resulting over-activation of the mammalian target of rapamycin (mTOR) signalling pathway leaves patients with TSC susceptible to the growth of non-malignant tumours in multiple organs. Previously, surgery was the main therapeutic option for TSC. However, pharmacological therapy with mTOR inhibitors such as everolimus and sirolimus is now emerging as an alternate approach. Everolimus and sirolimus have already been shown to be effective in treating subependymal giant cell astrocytoma (SEGA) and renal angiomyolipoma (AML), and everolimus is currently being evaluated in treating TSC-related epilepsy. In November 2013 a group of European experts convened to discuss the current options and practical considerations for treating various manifestations of TSC. This article provides evidence-based recommendations for the treatment of SEGA, TSC-related epilepsy and renal AML, with a focus on where mTOR inhibitor therapy may be considered alongside other treatment options. Safety considerations regarding mTOR inhibitor therapy are also reviewed. With evidence of beneficial effects in neurological and non-neurological TSC manifestations, mTOR inhibitors may represent a systemic treatment for TSC.