Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

被引:189
作者
Marra, Monica [1 ]
Sordelli, Ignazio M. [2 ]
Lombardi, Angela [1 ]
Lamberti, Monica [3 ]
Tarantino, Luciano [4 ]
Giudice, Aldo [5 ]
Stiuso, Paola [1 ]
Abbruzzese, Alberto [1 ]
Sperlongano, Rossella [2 ]
Accardo, Marina [6 ]
Agresti, Massimo [2 ]
Caraglia, Michele [1 ]
Sperlongano, Pasquale [2 ]
机构
[1] Univ Naples 2, Dept Biochem & Biophys, Naples, Italy
[2] Univ Naples 2, Dept Anaesthesiol & Special Surg, Naples, Italy
[3] Univ Naples 2, Dept Expt Med, Sez Med Iavoro Igiene & Tossicol Ind, Naples, Italy
[4] S Giovanni di Dio Hosp, Intervent US Unit, Dept Med, I-80059 Torre Del Greco, Naples, Italy
[5] Natl Inst Tumours Fdn G Pascale Naples, Anim Facil Unit, Naples, Italy
[6] Univ Naples 2, Dept Morphopathol, Naples, Italy
关键词
HEPATITIS-B-VIRUS; SIGNAL-REGULATED KINASE; GROWTH-FACTOR RECEPTOR; HCV CORE PROTEIN; PRIMARY LIVER-CANCER; NITRIC-OXIDE; REACTIVE OXYGEN; ENDOPLASMIC-RETICULUM; DOWN-REGULATION; BETA-CATENIN;
D O I
10.1186/1479-5876-9-171
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
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页数:14
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