title: Oncolytic virotherapy with modified adenoviruses and novel therapeutic targets.
abstract: BACKGROUND
  Numerous oncolytic viral mutants derived from a variety of strains have antitumor efficacy with limited or no toxicity to normal tissue. While all modes of administration were determined to be safe in patients with solid cancers refractory to current standard of care, this therapeutic approach requires further improvements to achieve definite efficacy.
  
  
  METHODS
  We review the most promising clinical developments with several oncolytic viruses. The focus is on preclinical and clinical findings with replication-selective adenoviral mutants including ONYX-015, H101 and Ad5ΔCR mutants that, to date, are the most studied oncolytic viruses. Cellular pathways reported to play a role in virus-induced cell killing are reviewed as potential targets for the development of more effective combinatorial therapies.
  
  
  CONCLUSIONS
  The most promising clinical outcomes for metastatic cancers have been reported for oncolytic vaccinia and herpes virus mutants expressing the cytokine GMCSF. However, highly efficacious and selective adenoviral mutants have been developed that interact synergistically with cytotoxic drugs in model systems. We anticipate that by delineating the cellular targets for synergistic cancer cell killing in response to adenoviral mutants and drugs such as apoptosis and autophagy signaling, greatly improved anticancer therapies will result in the near future.
authors.affiliation: Queen Mary University of London, Barts Cancer Institute, Centre for Molecular Oncology, London, UK.
authors.forename: Gunnel
authors.initials: G
authors.lastname: Halldén
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Portella
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses
chemical_list: D000970:Antineoplastic Agents