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Eur J Cancer. 2016 Jul;62:124-31. doi: 10.1016/j.ejca.2016.04.001. Epub 2016 May 31.

Implementation of mechanism of action biology-driven early drug development for children with cancer.

Author information

The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, London, UK. Electronic address:
Product Development Scientific Support Department, European Medicines Agency, Canary Wharf, London, UK.
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Centre for English Language Teaching, University of York, UK.
Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA.
Create for Chloe and UK representative for aPODD, UK.
Novartis Pharma AG, Basel CH-4002, Switzerland.
Hoffman-La Roche, Basel, Switzerland; Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Belgian Federal Agency for Medicines and Health Products, Brussels, Belgium.
Division of Clinical Studies, The Institute of Cancer Research, London, UK.
Department of Pediatric and Adolescent Oncology, Gustave Roussy, France.
Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, London, UK; Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), and Heidelberg University Hospital, Heidelberg 69120, Germany.
U830 INSERM, Recherche Translationelle en Oncologie Pédiatrique (RTOP) and Department of Pediatric Oncology, Institut Curie, Paris, France.
TetraLogic Pharmaceuticals, Malvern, PA 19355, USA.
aPODD Foundation, London, UK.
Department of Paediatric Oncology, Faculty of Medicine, University Hospital Brno and Masaryk University, Brno, Czech Republic; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, ICRC Brno, Brno, Czech Republic.
Boehringer Ingelheim, Germany.
Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Paediatric Haematology/Oncology Unit, Antwerp University Hospital, Antwerp University, Belgium.
Department of Clinical Research, Institut Gustave Roussy, Paris-Sud University, Paris, France.
Gustave Roussy, France.
AstraZeneca, USA.
Novartis, USA.


An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly.


Mechanism of action; Paediatric oncology; Targeted cancer drug development

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