Matter Matthias S, Decaens Thomas, Andersen Jesper B, Thorgeirsson Snorri S
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA.
J Hepatol. 2014 Apr;60(4):855-65. doi: 10.1016/j.jhep.2013.11.031. Epub 2013 Dec 3.
Mechanistic target of rapamycin (mTOR) regulates cell growth, metabolism and aging in response to nutrients, cellular energy stage and growth factors. mTOR is frequently up-regulated in cancer including hepatocellular carcinoma (HCC) and is associated with bad prognosis, poorly differentiated tumors, and earlier recurrence. Blocking mTOR with rapamycin and first generation mTOR inhibitors, called rapalogs, has shown promising reduction of HCC tumor growth in preclinical models. Currently, rapamycin/rapalogs are used in several clinical trials for the treatment of advanced HCC, and as adjuvant therapy in HCC patients after liver transplantation and TACE. A second generation of mTOR pathway inhibitors has been developed recently and is being tested in various clinical trials of solid cancers, and has been used in preclinical HCC models. The results of series of clinical trials using mTOR inhibitors in HCC treatment will emerge in the near future.
雷帕霉素的作用靶点（mTOR）可根据营养物质、细胞能量状态和生长因子来调节细胞生长、代谢及衰老。mTOR在包括肝细胞癌（HCC）在内的多种癌症中常呈上调状态，且与预后不良、肿瘤分化差及早期复发相关。在临床前模型中，用雷帕霉素及第一代mTOR抑制剂（即雷帕霉素类似物）阻断mTOR已显示出有望减少HCC肿瘤生长。目前，雷帕霉素/雷帕霉素类似物正用于多项治疗晚期HCC的临床试验，并作为肝移植和经动脉化疗栓塞术后HCC患者辅助治疗。第二代mTOR通路抑制剂最近已研发出来，正在实体癌的各种临床试验中进行测试，并已用于临床前HCC模型。使用mTOR抑制剂治疗HCC的一系列临床试验结果将在不久后公布。
