Moreno, Lucas, Barone, Giuseppe, DuBois, Steven G., Molenaar, Jan, Fischer, Matthias, Schulte, Johannes, Eggert, Angelika ORCID: 0000-0003-3476-8184, Schleiermacher, Gudrun, Speleman, Frank, Chesler, Louis, Geoerger, Birgit, Hogarty, Michael D., Irwin, Meredith S., Bird, Nick, Blanchard, Guy B., Buckland, Sean, Caron, Hubert, Davis, Susan, De Wilde, Bram, DeubZer, Hedwig E., Dolman, Emmy, Eilers, Martin, George, Rani E., George, Sally, Sterba, Jaroslav, Maris, John M., Marshall, Lynley, Merchant, Melinda, Mortimer, Peter, Owens, Cormac, Philpott, Anna, Poon, Evon, Shay, Jerry W., Tonelli, Roberto, Valteau-Couanet, Dominique, Vassal, Gilles, Park, Julie R. and Pearson, Andrew D. J. (2020). 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. Eur. J. Cancer, 136. S. 52 - 69. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

Full text not available from this repository.

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. (C) 2020 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Moreno, LucasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barone, GiuseppeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DuBois, Steven G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molenaar, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggert, AngelikaUNSPECIFIEDorcid.org/0000-0003-3476-8184UNSPECIFIED
Schleiermacher, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speleman, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chesler, LouisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geoerger, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogarty, Michael D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irwin, Meredith S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bird, NickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanchard, Guy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buckland, SeanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caron, HubertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Wilde, BramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DeubZer, Hedwig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dolman, EmmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eilers, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, Rani E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, SallyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sterba, JaroslavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maris, John M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marshall, LynleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merchant, MelindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mortimer, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owens, CormacUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Philpott, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poon, EvonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shay, Jerry W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tonelli, RobertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valteau-Couanet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vassal, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Julie R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearson, Andrew D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-322279
DOI: 10.1016/j.ejca.2020.05.010
Journal or Publication Title: Eur. J. Cancer
Volume: 136
Page Range: S. 52 - 69
Date: 2020
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1879-0852
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HIGH-RISK NEUROBLASTOMA; PHASE-I TRIAL; SOLID TUMORS; OPEN-LABEL; REFRACTORY NEUROBLASTOMA; INHIBITOR PF-06463922; THERAPEUTIC TARGET; REPLICATION STRESS; FREE SURVIVAL; RNAI SCREENMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32227

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item