Rochelle Bagatell1, Susan L Cohn. 1. 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.
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.
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.
Authors: Jan J Molenaar; Jan Koster; Danny A Zwijnenburg; Peter van Sluis; Linda J Valentijn; Ida van der Ploeg; Mohamed Hamdi; Johan van Nes; Bart A Westerman; Jennemiek van Arkel; Marli E Ebus; Franciska Haneveld; Arjan Lakeman; Linda Schild; Piet Molenaar; Peter Stroeken; Max M van Noesel; Ingrid Ora; Evan E Santo; Huib N Caron; Ellen M Westerhout; Rogier Versteeg Journal: Nature Date: 2012-02-22 Impact factor: 49.962
Authors: Alexei L Polishchuk; Richard Li; Christine Hill-Kayser; Anthony Little; Randall A Hawkins; Jeffrey Hamilton; Michael Lau; Hung Chi Tran; Caron Strahlendorf; Richard S Lemons; Vivian Weinberg; Katherine K Matthay; Steven G DuBois; Karen J Marcus; Rochelle Bagatell; Daphne A Haas-Kogan Journal: Int J Radiat Oncol Biol Phys Date: 2014-05-24 Impact factor: 7.038
Authors: Katleen De Preter; Pieter Mestdagh; Joëlle Vermeulen; Fjoralba Zeka; Arlene Naranjo; Isabella Bray; Victoria Castel; Caifu Chen; Elzbieta Drozynska; Angelika Eggert; Michael D Hogarty; Ewa Izycka-Swieszewska; Wendy B London; Rosa Noguera; Marta Piqueras; Kenneth Bryan; Benjamin Schowe; Peter van Sluis; Jan J Molenaar; Alexander Schramm; Johannes H Schulte; Raymond L Stallings; Rogier Versteeg; Geneviève Laureys; Nadine Van Roy; Frank Speleman; Jo Vandesompele Journal: Clin Cancer Res Date: 2011-10-26 Impact factor: 12.531
Authors: J A Kohler; H Rubie; V Castel; K Beiske; K Holmes; C Gambini; F Casale; C Munzer; G Erminio; S Parodi; S Navarro; C Marquez; M Peuchmaur; C Cullinane; P Brock; D Valteau-Couanet; A Garaventa; R Haupt Journal: Eur J Cancer Date: 2013-07-29 Impact factor: 9.162
Authors: Nai-Kong V Cheung; Jinghui Zhang; Charles Lu; Matthew Parker; Armita Bahrami; Satish K Tickoo; Adriana Heguy; Alberto S Pappo; Sara Federico; James Dalton; Irene Y Cheung; Li Ding; Robert Fulton; Jianmin Wang; Xiang Chen; Jared Becksfort; Jianrong Wu; Catherine A Billups; David Ellison; Elaine R Mardis; Richard K Wilson; James R Downing; Michael A Dyer Journal: JAMA Date: 2012-03-14 Impact factor: 56.272
Authors: Katherine K Matthay; C Patrick Reynolds; Robert C Seeger; Hiroyuki Shimada; E Stanton Adkins; Daphne Haas-Kogan; Robert B Gerbing; Wendy B London; Judith G Villablanca Journal: J Clin Oncol Date: 2009-01-26 Impact factor: 44.544
Authors: John M Maris; Christopher L Morton; Richard Gorlick; E Anders Kolb; Richard Lock; Hernan Carol; Stephen T Keir; C Patrick Reynolds; Min H Kang; Jianrong Wu; Malcolm A Smith; Peter J Houghton Journal: Pediatr Blood Cancer Date: 2010-07-15 Impact factor: 3.167
Authors: B De Bernardi; V Mosseri; H Rubie; V Castel; A Foot; R Ladenstein; G Laureys; M Beck-Popovic; A F de Lacerda; A D J Pearson; J De Kraker; P F Ambros; Y de Rycke; M Conte; P Bruzzi; J Michon Journal: Br J Cancer Date: 2008-09-02 Impact factor: 7.640
Authors: Clare J Twist; Mary Lou Schmidt; Arlene Naranjo; Wendy B London; Sheena C Tenney; Araz Marachelian; Hiroyuki Shimada; Margaret H Collins; Natia Esiashvili; E Stanton Adkins; Peter Mattei; Michael Handler; Howard Katzenstein; Edward Attiyeh; Michael D Hogarty; Julie Gastier-Foster; Elizabeth Wagner; Katherine K Matthay; Julie R Park; John M Maris; Susan L Cohn Journal: J Clin Oncol Date: 2019-08-06 Impact factor: 44.544
Authors: Martin Michaelis; Mark N Wass; Ian Reddin; Yvonne Voges; Florian Rothweiler; Stephanie Hehlgans; Jaroslav Cinatl; Marco Mernberger; Andrea Nist; Thorsten Stiewe; Franz Rödel; Jindrich Cinatl Journal: Cancers (Basel) Date: 2020-04-26 Impact factor: 6.639