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

Monica Marra1, Ignazio M Sordelli2, Angela Lombardi1, Monica Lamberti3, Luciano Tarantino4, Aldo Giudice5, Paola Stiuso1, Alberto Abbruzzese1, Rossella Sperlongano2, Marina Accardo6, Massimo Agresti2, Michele Caraglia1* and Pasquale Sperlongano2

Author Affiliations

1 Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy

2 Department of Anaesthesiology and Special Surgery, Second University of Naples, Naples, Italy

3 Departement of Experimental Medicine, Sezione di Medicina del lavoro, Igiene e Tossicologia Industriale, Second University of Naples, Naples, Italy

4 Interventional US Unit, Department of Medicine, S. Giovanni di Dio Hospital, 80059 Torre del Greco (Naples), Italy

5 Animal Facility Unit, National Institute of Tumours "Fondazione G. Pascale" of Naples, Naples, Italy

6 Department of Morphopathology, II University Naples, Napoli, Italy

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Journal of Translational Medicine 2011, 9:171  doi:10.1186/1479-5876-9-171

Published: 10 October 2011


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.