title: Cytokines for the treatment of gastrointestinal cancers: clinical experience and new perspectives.
abstract: BACKGROUND
  Cytokines are key mediators of the immune system and have been proposed as therapeutic agents against cancer, either as recombinant proteins, or as transgenes in gene therapy approaches. Stimulation of immune responses against cancer cells is an appealing method to treat tumors with high risk of relapse and systemic dissemination.
  
  
  METHODS
  We provide a critical overview of clinical trials involving the use of cytokines for the treatment of liver, colon and pancreatic cancers. Special attention has been paid to advances in the field of gene therapy and oncolytic viruses. The potential of new developments still in a pre-clinical stage is also discussed. We have revised public sources of information (PubMed, US National Institutes of Health clinical trials database) up to January 2013.
  
  
  CONCLUSIONS
  The complexity of the immune system and the unfavorable pharmacokinetic properties of cytokines limit the efficacy of these molecules as single agents for the treatment of cancer. Expression from gene therapy vectors, together with new methods of targeting and stabilization, may overcome these hurdles. We believe cytokines will play a crucial role as part of combined approaches, enhancing the action of adoptive cell immunotherapy, oncolytic viruses or biological therapies.
authors.affiliation: CIMA, University of Navarra, Division of Hepatology and Gene Therapy, Foundation for Applied Medical Research, Pamplona, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Hernandez-Alcoceba
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
authors.forename: Gloria
authors.initials: G
authors.lastname: Gonzalez-Aseguinolaza
authors.forename: Jesus
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines