Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
J Transl Med. 2011 Oct 10;9:171. doi: 10.1186/1479-5876-9-171.
Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV). Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase. The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients. The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC.
肝细胞癌（HCC）是一种复杂的异质性肿瘤，具有多种基因异常。参与调节增殖和细胞死亡的几个分子途径与肝癌的发生有关。HCC 的主要病因因素是乙型肝炎病毒（HBV）和丙型肝炎病毒感染（HCV）。持续的氧化应激，由环境因素或细胞线粒体功能障碍产生的活性氧（ROS）引起，最近与肝癌的发生有关。另一方面，HCC 的一个独特的病理标志是构成最重要的自由基清除系统的氧化还原酶的急剧下调，这些酶由过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶代表。多激酶抑制剂索拉非尼是最有前途的靶向药物，已在晚期 HCC 患者的 III 期临床试验中进行了广泛研究。与其他基于靶向的药物联合使用可能会增强索拉非尼单独使用的临床获益。事实上，一项 II 期多中心研究表明，索拉非尼和奥曲肽 LAR（So.LAR 方案）联合在晚期 HCC 患者中具有活性且耐受性良好。检测对索拉非尼等抗癌药物有反应的分子因素，以及鉴定对抗癌药物的耐药机制，可能代表改善 HCC 治疗的方向。
