title: Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview.
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.
authors: Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
authors: Monica
authors: M
authors: Marra
authors: Ignazio M
authors: IM
authors: Sordelli
authors: Angela
authors: A
authors: Lombardi
authors: Monica
authors: M
authors: Lamberti
authors: Luciano
authors: L
authors: Tarantino
authors: Aldo
authors: A
authors: Giudice
authors: Paola
authors: P
authors: Stiuso
authors: Alberto
authors: A
authors: Abbruzzese
authors: Rossella
authors: R
authors: Sperlongano
authors: Marina
authors: M
authors: Accardo
authors: Massimo
authors: M
authors: Agresti
authors: Michele
authors: M
authors: Caraglia
authors: Pasquale
authors: P
authors: Sperlongano
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018384:Oxidative Stress
chemical_list: D014408:Biomarkers, Tumor