title: Gene therapy for cisplatin-induced ototoxicity: a systematic review of in vitro and experimental animal studies.
abstract: OBJECTIVE
  Ototoxicity is a frequent adverse event of cisplatin treatment. No therapy is currently available for cisplatin-induced ototoxicity. A systematic review of experimental animal studies and in vitro experiments was conducted to evaluate gene therapy as a potential future therapeutic option.
  
  
  METHODS
  Eligible studies were identified through searches of electronic databases Ovid MEDLINE, Ovid MEDLINE In-Process, Embase, PubMed, Biosis Previews, Scopus, ISI Web of Science, and The Cochrane Library.
  
  
  METHODS
  Articles obtained from the search were independently reviewed by 2 authors using specific criteria to identify experimental animal studies and in vitro experiments conducted to evaluate gene therapy for cisplatin-induced ototoxicity. No restriction was applied to publication dates or languages.
  
  
  METHODS
  Data extracted included experiment type, cell type, species, targeted gene, gene expression, method, administration, inner ear site evaluated, outcome measures for cytotoxicity, and significant results.
  
  
  RESULTS
  Fourteen articles were included in this review. In vitro and in vivo experiments have been performed to evaluate the potential of gene expression manipulation for cisplatin-induced ototoxicity. Twelve different genes were targeted including NTF3, GDNF, HO-1, XIAP, Trpv1, BCL2, Otos, Nfe2l2, Nox1, Nox3, Nox4, and Ctr1. All of the included articles demonstrated a benefit of gene therapy on cytotoxicity caused by cisplatin.
  
  
  CONCLUSIONS
  Experimental animal studies and in vitro experiments have demonstrated the efficacy of gene therapy for cisplatin-induced ototoxicity. However, further investigation regarding safety, immunogenicity, and consequences of genetic manipulation in the inner ear tissues must be completed to develop future therapeutic options.
authors.affiliation: McGill Auditory Sciences Laboratory, McGill University, Montreal, Quebec, Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Waissbluth
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitaro
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Daniel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002945:Cisplatin / Q000009:adverse effects*; D018390:Gene Targeting; D015316:Genetic Therapy; D005822:Genetic Vectors; D006311:Hearing Disorders / Q000139:chemically induced* / Q000628:therapy*; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D009414:Nerve Growth Factors / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011506:Proteins / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009414:Nerve Growth Factors; C503045:OTOS protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D002945:Cisplatin