Faculty of Medicine and Surgery, University of Verona, 37134 Verona, Italy.
Department of Surgery, University of Illinois Chicago, Chicago, IL 60607, USA.
Curr Oncol. 2023 Jun 9;30(6):5574-5592. doi: 10.3390/curroncol30060421.
Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.
肝移植是治疗早期不可切除 HCC 患者的一种选择，当满足米兰标准时具有更大的优势。为了降低移植后移植物排斥的风险，需要使用免疫抑制方案，而在这种情况下，CNI 是首选药物。然而，它们对 T 细胞活性的抑制作用导致肿瘤复发的风险更高。mTOR 抑制剂（mTORi）已被引入作为替代传统 CNI 为基础的方案的免疫抑制方法，以解决免疫抑制和癌症控制的问题。PI3K-AKT-mTOR 信号通路调节蛋白质翻译、细胞生长和代谢，该通路在人类肿瘤中经常失调。几项研究表明 mTORi 在减少 LT 后 HCC 进展中的作用，其复发率较低。此外，mTOR 免疫抑制控制与 CNI 暴露相关的肾损伤。转换为 mTOR 抑制剂与稳定和恢复肾功能有关，提示具有重要的肾保护作用。这种治疗方法的局限性与它们对脂质和葡萄糖代谢以及蛋白尿发展和伤口愈合的负面影响有关。本文旨在总结 mTORi 在管理接受 LT 的 HCC 患者中的作用。还提出了克服常见不良反应的策略。
