@article{51bfa813017a4100a4427e1819b143a7,
title = "Accelerating drug development for neuroblastoma: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma",
abstract = "Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy.",
keywords = "Clinical trials, Drug development, Epigenetics, MYCN, Neuroblastoma, Phase I, Preclinical testing",
author = "Lucas Moreno and Giuseppe Barone and DuBois, {Steven G.} and Jan Molenaar and Matthias Fischer and Johannes Schulte and Angelika Eggert and Gudrun Schleiermacher and Frank Speleman and Louis Chesler and Birgit Geoerger and Hogarty, {Michael D.} and Irwin, {Meredith S.} and Nick Bird and Blanchard, {Guy B.} and Sean Buckland and Hubert Caron and Susan Davis and {De Wilde}, Bram and Deubzer, {Hedwig E.} and Emmy Dolman and Martin Eilers and George, {Rani E.} and Sally George and {\v S}t{\v e}rba Jaroslav and Maris, {John M.} and Lynley Marshall and Melinda Merchant and Peter Mortimer and Cormac Owens and Anna Philpott and Evon Poon and Shay, {Jerry W.} and Roberto Tonelli and Dominique Valteau-Couanet and Gilles Vassal and Park, {Julie R.} and Pearson, {Andrew D.J.}",
note = "Funding Information: Funding for the NDDS initiative and meeting from Neuroblastoma UK and Smile With Siddy . Lucas Moreno was funded by the Oak Foundation and Instituto de Salud Carlos III (Juan Rodes research fellowship JR15/00041). Steven DuBois was funded by an Alex's Lemonade Stand Foundation Center of Excellence grant. Frank Speleman was funded by FWO Vlaanderen (fund for scientific research Flanders) (post)doctoral grant 12U4718N ; Olivia Hendrickx Research Fund ; Kom op tegen kanker ; Stichting tegen kanker ( 2018-125 ). John Maris was funded by R35 grant: NCI R35 CA 220500. Lynley Marshall was funded by the Oak Foundation. The authors thank Gynette Cook for help with the preparation of the workshop and manuscript. Funding Information: Funding for the NDDS initiative and meeting from Neuroblastoma UK and Smile With Siddy. Lucas Moreno was funded by the Oak Foundation and Instituto de Salud Carlos III (Juan Rodes research fellowship JR15/00041). Steven DuBois was funded by an Alex's Lemonade Stand Foundation Center of Excellence grant. Frank Speleman was funded by FWO Vlaanderen (fund for scientific research Flanders) (post)doctoral grant 12U4718N; Olivia Hendrickx Research Fund; Kom op tegen kanker; Stichting tegen kanker (2018-125). John Maris was funded by R35 grant: NCI R35 CA 220500. Lynley Marshall was funded by the Oak Foundation. The authors thank Gynette Cook for help with the preparation of the workshop and manuscript. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = sep,
doi = "10.1016/j.ejca.2020.05.010",
language = "English (US)",
volume = "136",
pages = "52--68",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}