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Review
. 2016 Feb;28(1):19-25.
doi: 10.1097/MOP.0000000000000296.

Genetic discoveries and treatment advances in neuroblastoma

Rochelle Bagatell  1 , Susan L Cohn
Affiliations
Review

Genetic discoveries and treatment advances in neuroblastoma

Rochelle Bagatell et al. Curr Opin Pediatr. 2016 Feb.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

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Conflict of interest statement

Conflicts of Interest

Susan L. Cohn: Equity ownership: United Therapeutics, Pfizer, Novartis United Therapeutics Advisory Board

Figures

Figure 1
Figure 1
Probability of event-free survival (EFS) (A) and overall survival (OS) (B) among 3,352 Children's Oncology Group (COG) patients with high-risk neuroblastoma diagnosed between 1990 and 2010 according to era. 356 patients were diagnosed between 1990 and 1994; 497 were diagnosed from 1995 to 1999; 1,105 were diagnosed from 2000 to 2004, and 1,484 were diagnosed from 2005 to 2010. (Data provided by the COG Statistics and Data Center.) (Reused with permission. © 2015 American Society of Clinical Oncology. All rights reserved. Pinto NR, et al.: J Clin Oncol. 2015 Aug 24. pii: JCO.2014.59.4648. [Epub ahead of print])
See this image and copyright information in PMC

References

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