mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation?
mTOR inhibitor therapy: Does it prevent HCC recurrence after liver transplantation?
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DOI：
10.1016/j.trre.2015.02.003
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发表时间：
2015-07-01
影响因子：
4
通讯作者：
Toso, Christian
中科院分区：
文献类型：
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作者：
Duvoux, Christophe;Toso, Christian
预防肝移植后肝细胞癌（HCC）复发是临床重点。哺乳动物雷帕霉素（mTOR）通路在细胞生长和存活中的重要性，使其成为抗肿瘤策略的逻辑靶点，在各种类型的恶性肿瘤的临床数据中得到证实。多项研究表明，mTOR抑制剂依维莫司和西罗莫司在HCC动物模型中抑制细胞增殖和肿瘤生长。联合使用mTOR抑制剂可以降低化疗药物在HCC治疗中的剂量，在非移植HCC人群中的试验正在探索与各种药物联合使用，包括索拉非尼、血管内皮生长因子抑制剂贝伐单抗和传统药物。在肝移植后的预防作用方面，回顾性研究和非随机前瞻性分析的数据表明，与标准的钙调磷酸酶抑制剂方案相比，接受mTOR抑制剂联合钙调磷酸酶抑制剂治疗的患者HCC复发率和总生存率可能会提高。荟萃分析支持了这些发现，但在得出任何确定的结论之前，还需要进行对照试验。在评估肝移植后重新使用mTOR抑制剂治疗的三个随机试验中，有两个试验在移植后1年接受mTOR抑制剂治疗的患者的HCC复发率在数值上低于对照组，但绝对数字较低。总的来说，根据回顾性研究、荟萃分析和随机试验事后评估的现有数据，HCC移植后考虑基于mTOR抑制的免疫抑制似乎是可取的，特别是在超过米兰标准的患者中。等待前瞻性数据。(C) 2015爱思唯尔公司版权所有。
Prevention of hepatocellular carcinoma (HCC) recurrence after liver transplantation is a clinical priority. The importance of the mammalian target of rapamycin (mTOR) pathway in cell growth and survival makes it a logical target for antitumor strategies, as borne out by clinical data in various types of malignancy. A number of studies have indicated that the mTOR inhibitors everolimus and sirolimus suppress cell proliferation and tumor growth in animal models of HCC. Coadministration of an mTOR inhibitor could permit lower dosing of chemotherapeutic agents in HCC management, and trials in non-transplant HCC population are exploring combined used with various agents including sorafenib, the vascular endothelial growth factor inhibitor bevacizumab and conventional agents. In terms of a preventive effect after liver transplantation for HCC, data from retrospective studies and non-randomized prospective analyses in which patients received an mTOR inhibitor with concomitant calcineurin inhibitor therapy have indicated that HCC recurrence rates and overall survival may be improved compared to a standard calcineurin inhibitor regimen. Meta-analyses have supported these findings, but controlled trials are required before any firm conclusions can be drawn. In two of the three randomized trials which have assessed de novo mTOR inhibitor therapy after liver transplantation, there was a numerically lower rate of HCC recurrence by one year post-transplant in patients given an mTOR inhibitor versus the control arm, but absolute numbers were low. Overall, based on the available data from retrospective studies, meta-analyses, and post-hoc assessments of randomized trials, it appears advisable to consider mTOR inhibition-based immunosuppression after transplantation for HCC, particularly in patients who exceed the Milan criteria. Prospective data are awaited. (C) 2015 Elsevier Inc. All rights reserved.