title: Therapeutic targets for neuroblastomas.
abstract: BACKGROUND
  Neuroblastoma (NB) is the most common and deadly solid tumor in children. Despite recent improvements, the long-term outlook for high-risk NB is still < 50%. Further, there is considerable short- and long-term toxicity. More effective, less toxic therapy is needed, and the development of targeted therapies offers great promise.
  
  
  METHODS
  Relevant literature was reviewed to identify current and future therapeutic targets that are critical to malignant transformation and progression of NB. The potential or actual NB therapeutic targets are classified into four categories: i) genes activated by amplification, mutation, translocation or autocrine overexpression; ii) genes inactivated by deletion, mutation or epigenetic silencing; iii) membrane-associated genes expressed on most NBs but few other tissues; or iv) common target genes relevant to NB as well as other tumors.
  
  
  CONCLUSIONS
  Therapeutic approaches have been developed to some of these targets, but many remain untargeted at the present time. It is unlikely that single targeted agents will be sufficient for long-term cure, at least for high-risk NBs. The challenge will be how to integrate targeted agents with each other and with conventional therapy to enhance their efficacy, while simultaneously reducing systemic toxicity.
authors.affiliation: Children's Hospital of Philadelphia, Division of Oncology , CTRB Rm. 3018, 3501 Civic Center Blvd., Philadelphia, PA 19104-4302 , USA +1 215 590 2817 ; +1 215 590 3770 ; Brodeur@email.chop.edu.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Brodeur
authors.forename: Radhika
authors.initials: R
authors.lastname: Iyer
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Croucher
authors.forename: Tiangang
authors.initials: T
authors.lastname: Zhuang
authors.forename: Mayumi
authors.initials: M
authors.lastname: Higashi
authors.forename: Venkatadri
authors.initials: V
authors.lastname: Kolla
mesh_terms: D000818:Animals; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D009154:Mutation; D009423:Nervous System Neoplasms / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*