title: Progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) carries a dismal prognosis, with advanced disease being resistant to both radiotherapy and conventional cytotoxic drugs, whilst anti-angiogenic drugs are marginally efficacious. Oncolytic viruses (OVs) offer the promise of selective cancer therapy through direct and immune-mediated mechanisms. The premise of OVs lies in their preferential genomic replication, protein expression and productive infection of malignant cells. Numerous OVs are being tested in preclinical models of HCC, with good evidence of direct and immune-mediated anti-tumour efficacy. Efforts to enhance the performance of these agents have concentrated on engineering OV cellular specificity, immune evasion, enhancing anti-tumour potency and improving delivery. The lead agent in HCC clinical trials, JX-594, a recombinant Wyeth strain vaccinia virus, has demonstrated evidence for significant benefit and earned orphan drug status. Thus, JX-594 appears to be transcending the barrier between novel laboratory science and credible clinical therapy. Relatively few other OVs have entered clinical testing, a hurdle that must be overcome if significant progress is to be made in this field. This review summarizes the preclinical and clinical experience of OV therapy in the difficult-to-treat area of HCC.
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK.
authors.forename: Adel H
authors.initials: AH
authors.lastname: Jebar
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Errington-Mais
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 4Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA 3Department of Molecular Medicine, Institute of Cancer Research, London, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Vile
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Melcher
authors.affiliation: 1Leeds Institute of Cancer and Pathology (LICAP), Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK 2Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, St James' University Hospital, University of Leeds, West Yorkshire, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Griffin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods* / Q000639:trends*; D050504:Oncolytic Viruses / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D009965:Orphan Drug Production; D014616:Vaccinia virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology
chemical_list: D000998:Antiviral Agents