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
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
Grant support
25636
Cancer Research UK - United Kingdom
R01 CA197336
NCI NIH HHS - United States
PubMed
32653773
DOI
10.1016/j.ejca.2020.05.010
PII: S0959-8049(20)30276-8
Knihovny.cz E-resources
- Keywords
- Clinical trials, Drug development, Epigenetics, MYCN, Neuroblastoma, Phase I, Preclinical testing,
- MeSH
- Molecular Targeted Therapy methods trends MeSH
- Child MeSH
- Therapies, Investigational methods trends MeSH
- Protein Kinase Inhibitors isolation & purification therapeutic use MeSH
- Congresses as Topic MeSH
- Medical Oncology methods organization & administration trends MeSH
- Humans MeSH
- Brain Neoplasms drug therapy pathology MeSH
- Neuroblastoma drug therapy pathology MeSH
- Drug Discovery methods organization & administration trends MeSH
- Pediatrics methods organization & administration trends MeSH
- Antineoplastic Agents isolation & purification therapeutic use MeSH
- Drug Development * methods organization & administration trends MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Geographicals
- Europe MeSH
- Names of Substances
- Protein Kinase Inhibitors MeSH
- Antineoplastic Agents MeSH
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.
Center for Medical Genetics Ghent Belgium
Center for Molecular Medicine Cologne Medical Faculty University of Cologne Cologne Germany
Department of Biochemistry and Molecular Biology University of Wuerzburg Germany
Department of Cell Biology UT Southwestern Medical Center Dallas TX USA
Department of Clinical Research Gustave Roussy Paris Sud University Paris France
Department of Oncology University of Cambridge UK
Department of Paediatric Haemaology Oncology Our Lady's Children's Hospital Dublin Ireland
Department of Paediatric Oncology Great Ormond Street Hospital for Children London UK
Department of Pediatric Oncology and Hematology Charité University Hospital Berlin Germany
Department of Pharmacy and Biotechnology University of Bologna Bologna Italy
Division of Clinical Studies and Cancer Therapeutics The Institute of Cancer Research Sutton UK
Hoffmann La Roche Ltd Basel Switzerland
Paediatric Haematology and Oncology Division Hospital Universitari Vall d'Hebron Barcelona Spain
Princess Máxima Centre for Paediatric Oncology Utrecht The Netherlands
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