非酒精性脂肪性肝病（NAFLD）患病率的不断上升，引起了全球肝细胞癌（HCC）高发病率的日益关注。 NAFLD 向 HCC 的进展是异质性和非线性的，涉及非酒精性脂肪性肝炎 (NASH)、肝纤维化和肝硬化的中间阶段。为了应对这一新出现的流行病，对适当的诊断、预后和治疗方案的临床需求尚未得到满足。不幸的是，目前还没有经过验证的标记物可以识别 NAFLD 或 NASH 患者患 HCC 的风险。此外，目前的 HCC 治疗方案无法区分 HCC 的病毒感染或 NAFLD 特异性病因，并且成功率有限。哺乳动物雷帕霉素靶蛋白复合物 1 (mTORc1) 是一种重要的蛋白质，参与许多重要的细胞过程，如脂质代谢、葡萄糖稳态和炎症。这些细胞过程与 NAFLD 及其进展为严重肝脏表现密切相关。此外，已知 mTORc1 的过度激活会促进细胞增殖，从而促进肿瘤的发生和进展。许多 mTORc1 抑制剂正在不同阶段的临床试验中针对不同类型的癌症进行评估。本文探讨了 mTORc1 信号通路在 NAFLD 及其进展为 NASH 和 HCC 中的强烈病理学意义，并主张在具有 NAFLD/NASH 特异性病因的 HCC 合适的临床前模型中对已知的 mTORc1 抑制剂进行系统研究。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) is a growing concern for the high incidence rate of hepatocellular carcinoma (HCC) globally. The progression of NAFLD to HCC is heterogeneous and non-linear, involving intermediate stages of non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. There is a high unmet clinical need for appropriate diagnostic, prognostic, and therapeutic options to tackle this emerging epidemic. Unfortunately, at present, there is no validated marker to identify the risk of developing HCC in patients suffering from NAFLD or NASH. Additionally, the current treatment protocols for HCC don't differentiate between viral infection or NAFLD-specific etiology of the HCC and have a limited success rate. The mammalian target of rapamycin complex 1 (mTORc1) is an important protein involved in many vital cellular processes like lipid metabolism, glucose homeostasis, and inflammation. These cellular processes are highly implicated in NAFLD and its progression to severe liver manifestations. Additionally, hyperactivation of mTORc1 is known to promote cell proliferation, which can contribute to the genesis and progression of tumors. Many mTORc1 inhibitors are being evaluated for different types of cancers under various phases of clinical trials. This paper deliberates on the strong pathological implication of the mTORc1 signaling pathway in NAFLD and its progression to NASH and HCC and advocates for a systematic investigation of known mTORc1 inhibitors in suitable pre-clinical models of HCC having NAFLD/NASH-specific etiology.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.