title: Genetic discoveries and treatment advances in neuroblastoma.
abstract: OBJECTIVE
  Major advances in our understanding of the genetic basis of neuroblastoma, and the role somatic alterations play in driving tumor growth, have led to improvements in risk-stratified therapy and have provided the rationale for targeted therapies. In this review, we highlight current risk-based treatment approaches and discuss the opportunities and challenges of translating recent genomic discoveries into the clinic.
  
  
  RESULTS
  Significant progress in the treatment of neuroblastoma has been realized using risk-based treatment strategies. Outcome has improved for all patients, including those classified as high-risk, although survival remains poor for this cohort. Integration of whole-genome DNA copy number and comprehensive molecular profiles into neuroblastoma classification systems will allow more precise prognostication and refined treatment assignment. Promising treatments that include targeted systemic radiotherapy, pathway-targeted small molecules, and therapy targeted at cell surface molecules are being evaluated in clinical trials, and recent genomic discoveries in relapsed tumor samples have led to the identification of new actionable mutations.
  
  
  CONCLUSIONS
  The integration of refined treatment stratification based on whole-genome profiles with therapeutics that target the molecular drivers of malignant behavior in neuroblastoma has the potential to dramatically improve survival, with decreased toxicity.
authors.affiliation: aDivision of Oncology, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania bDepartment of Pediatrics, Comer Children's Hospital, University of Chicago, Chicago, Illinois, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Bagatell
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
mesh_terms: D002648:Child; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009154:Mutation; D009447:Neuroblastoma / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D012008:Recurrence; D018570:Risk Assessment / Q000379:methods; D059467:Transcriptome