Yamashita Taro, Kaneko Shuichi
Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
Gan To Kagaku Ryoho. 2010 Jan;37(1):14-7.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. HCC nearly almost always develops in connection with chronic hepatitis or liver cirrhosis, mainly due to hepatitis B virus or hepatitis C virus infection. Several factors are supposed to play key roles in the development of HCC, such as aberrant viral protein expression, genomic instability with/without insertions of viral DNAs, gene mutations, epigenetic gene modification, oxidative stress, and alteration of the microenvironment including inflammation, fibrosis, and emergence of stem/progenitor cells as a result of repeated necrosis and regeneration of hepatocytes. The elucidation of molecular mechanisms of hepatocarcinogenesis has successfully provided small molecule inhibitors targeting aberrantly activated signaling in HCC. Development of novel classification systems based on the molecular profiles and drug sensitivities against molecularly targeted compounds is currently underway to facilitate novel strategies for effective eradication of HCC.
肝细胞癌(HCC)是全球第三大致癌死亡原因。HCC几乎总是与慢性肝炎或肝硬化相关,主要是由于乙型肝炎病毒或丙型肝炎病毒感染。一些因素被认为在HCC的发生发展中起关键作用,如异常的病毒蛋白表达、有无病毒DNA插入的基因组不稳定、基因突变、表观遗传基因修饰、氧化应激以及微环境的改变,包括炎症、纤维化以及由于肝细胞反复坏死和再生导致的干细胞/祖细胞的出现。对肝癌发生分子机制的阐明成功地提供了针对HCC中异常激活信号的小分子抑制剂。目前正在基于分子谱和对分子靶向化合物的药物敏感性开发新的分类系统,以促进有效根除HCC的新策略。