World J Gastroenterol. 2012 Aug 21;18(31):4071-81. doi: 10.3748/wjg.v18.i31.4071.
It has been established that cancer can be promoted and exacerbated by inflammation. Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and its long-term prognosis remains poor. Although HCC is a complex and heterogeneous tumor with several genomic mutations, it usually develops in the context of chronic liver damage and inflammation, suggesting that understanding the mechanism(s) of inflammation-mediated hepatocarcinogenesis is essential for the treatment and prevention of HCC. Chronic liver damage induces a persistent cycle of necro-inflammation and hepatocyte regeneration, resulting in genetic mutations in hepatocytes and expansion of initiated cells, eventually leading to HCC development. Recently, several inflammation- and stress-related signaling pathways have been identified as key players in these processes, which include the nuclear factor-κB, signal transducer and activator of transcription, and stress-activated mitogen- activated protein kinase pathways. Although these pathways may suggest potential therapeutic targets, they have a wide range of functions and complex crosstalk occurs among them. This review focuses on recent advances in our understanding of the roles of these signaling pathways in hepatocarcinogenesis.
已经证实，炎症可以促进和加剧癌症。肝细胞癌（HCC）是全球第五大常见癌症，其长期预后仍然较差。尽管 HCC 是一种具有多种基因组突变的复杂异质性肿瘤，但它通常在慢性肝损伤和炎症的背景下发展，这表明了解炎症介导的肝癌发生的机制对于 HCC 的治疗和预防至关重要。慢性肝损伤诱导持续的坏死-炎症和肝细胞再生循环，导致肝细胞发生基因突变和起始细胞的扩增，最终导致 HCC 的发展。最近，已经确定了几种与炎症和应激相关的信号通路作为这些过程中的关键参与者，其中包括核因子-κB、信号转导和转录激活因子以及应激激活的丝裂原激活的蛋白激酶通路。尽管这些通路可能提示潜在的治疗靶点，但它们具有广泛的功能，并且它们之间存在复杂的串扰。这篇综述重点介绍了我们对这些信号通路在肝癌发生中的作用的最新认识。
