title: Hepatocellular carcinoma: novel molecular targets in carcinogenesis for future therapies.
abstract: BACKGROUND
  Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy.
  
  
  METHODS
  A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: "hepatocellular carcinoma," "molecular hepatocarcinogenesis," "targeted therapy," and "immunotherapy."
  
  
  CONCLUSIONS
  Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.
authors.affiliation: Hepatology Unit, Department of Medical and Pediatric Sciences, University of Catania, Policlinic, Via Santa Sofia No. 78, 95123 Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bertino
authors.affiliation: Hepatology Unit, Department of Medical and Pediatric Sciences, University of Catania, Policlinic, Via Santa Sofia No. 78, 95123 Catania, Italy.
authors.forename: Shirin
authors.initials: S
authors.lastname: Demma
authors.affiliation: Hepatology Unit, Department of Medical and Pediatric Sciences, University of Catania, Policlinic, Via Santa Sofia No. 78, 95123 Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ardiri
authors.affiliation: Hepatology Unit, Department of Medical and Pediatric Sciences, University of Catania, Policlinic, Via Santa Sofia No. 78, 95123 Catania, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Proiti
authors.affiliation: Abdominal Transplantation Unit, ISMETT Palermo, UPMC-Italy, Via Ernesto Tricomi No. 5, 90127 Palermo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gruttadauria
authors.affiliation: Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Via Messina No. 829, 95126 Catania, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Toro
authors.affiliation: Research Centre "The Great Senescence", University of Catania, Via Messina No. 829, 95126 Catania, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Malaguarnera
authors.affiliation: Faculty of Pharmacy, University of Catania, Viale Andrea Doria No. 6, 95123 Catania, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bertino
authors.affiliation: Research Centre "The Great Senescence", University of Catania, Via Messina No. 829, 95126 Catania, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Malaguarnera
authors.affiliation: Research Centre "The Great Senescence", University of Catania, Via Messina No. 829, 95126 Catania, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Malaguarnera
authors.affiliation: Department of Surgical Sciences, Organ Transplantation and Advanced Technologies, University of Catania, Via Messina No. 829, 95126 Catania, Italy.
authors.forename: Isidoro
authors.initials: I
authors.lastname: Di Carlo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004722:Endoribonucleases / Q000378:metabolism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D042822:Genomic Instability; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C105937:GPC3 protein, human; D053673:Glypicans; D047428:Protein Kinase Inhibitors; D015534:Trans-Activators; D004722:Endoribonucleases; C466279:DCP1A protein, human
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