Department of Pediatrics, University of Alberta, Edmonton T6G 2S2, Canada.
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Andalucía Tech, Universidad de Málaga, Málaga 29071, Spain.
World J Gastroenterol. 2018 Sep 7;24(33):3695-3708. doi: 10.3748/wjg.v24.i33.3695.
Hepatocellular carcinoma (HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition receptor (c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microRNAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.
肝细胞癌（HCC）是第五种最常见的癌症，也是癌症死亡的第二大主要原因。由于 HCC 的诊断困难，在许多情况下，HCC 患者被诊断为晚期。肝细胞生长因子（HGF）/间质上皮转化受体（c-Met）轴是 HCC 的关键信号通路，无论是通过经典途径还是非经典途径。基于 HGF/c-Met 抑制的 HCC 可用治疗方法可以增加患者的寿命，但达不到预期的治疗效果。在 HCC 中，c-Met 单体可以与其他受体单体结合，激活几种非经典信号通路，导致细胞增殖、侵袭、迁移和耐药性增加。所有这些过程都受到肿瘤微环境的增强，基质细胞通过氧化应激、血管生成、淋巴管生成、炎症和纤维化来促进肿瘤进展。正在探索针对 HCC 的新治疗方法，以调节其他靶点，如 microRNAs、甲基转移酶和乙酰转移酶，这些靶点都参与了癌症中基因表达的调控。这篇综述汇集了关于 HCC 信号通路的基本知识，以及已经用于或显示出在临床试验中具有潜力的化合物。
