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

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Author(s): Marra Monica | Sordelli Ignazio | Lombardi Angela | Lamberti Monica | Tarantino Luciano | Giudice Aldo | Stiuso Paola | Abbruzzese Alberto | Sperlongano Rossella | Accardo Marina | Agresti Massimo | Caraglia Michele | Sperlongano Pasquale

Journal: Journal of Translational Medicine
ISSN 1479-5876

Volume: 9;
Issue: 1;
Start page: 171;
Date: 2011;
Original page

ABSTRACT
Abstract 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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