Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, 14004 Córdoba, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 14004 Córdoba, Spain.
Int J Mol Sci. 2020 Feb 13;21(4):1266. doi: 10.3390/ijms21041266.
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and occurs mainly in patients with liver cirrhosis. The mammalian target of rapamycin (mTOR) signaling pathway is involved in many hallmarks of cancer including cell growth, metabolism re-programming, proliferation and inhibition of apoptosis. The mTOR pathway is upregulated in HCC tissue samples as compared with the surrounding liver cirrhotic tissue. In addition, the activation of mTOR is more intense in the tumor edge, thus reinforcing its role in HCC proliferation and spreading. The inhibition of the mTOR pathway by currently available pharmacological compounds (i.e., sirolimus or everolimus) is able to hamper tumor progression both in vitro and in animal models. The use of mTOR inhibitors alone or in combination with other therapies is a very attractive approach, which has been extensively investigated in humans. However, results are contradictory and there is no solid evidence suggesting a true benefit in clinical practice. As a result, neither sirolimus nor everolimus are currently approved to treat HCC or to prevent tumor recurrence after curative surgery. In the present comprehensive review, we analyzed the most recent scientific evidence while providing some insights to understand the gap between experimental and clinical studies.
肝细胞癌（HCC）是最常见的原发性肝癌，主要发生在肝硬化患者中。雷帕霉素靶蛋白（mTOR）信号通路参与了许多癌症的标志性特征，包括细胞生长、代谢重编程、增殖和凋亡抑制。与周围肝硬化组织相比，HCC 组织样本中 mTOR 通路被上调。此外，mTOR 的激活在肿瘤边缘更为强烈，从而加强了其在 HCC 增殖和扩散中的作用。目前可用的药理学化合物（即西罗莫司或依维莫司）抑制 mTOR 通路能够在体外和动物模型中阻碍肿瘤进展。mTOR 抑制剂单独或与其他疗法联合使用是一种非常有吸引力的方法，已经在人类中进行了广泛的研究。然而，结果存在矛盾，没有确凿的证据表明在临床实践中有真正的益处。因此，西罗莫司和依维莫司目前均未被批准用于治疗 HCC 或预防根治性手术后的肿瘤复发。在本次全面综述中，我们分析了最新的科学证据，并提供了一些见解，以了解实验研究和临床研究之间的差距。
