Implementation of mechanism of action biology-driven early drug development for children with cancer.
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.
The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, London, UK. Electronic address: andy1pearson@btinternet.com.
Andrew D J
AD
Pearson
Product Development Scientific Support Department, European Medicines Agency, Canary Wharf, London, UK.
Ralf
R
Herold
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Raphaël
R
Rousseau
Centre for English Language Teaching, University of York, UK.
Chris
C
Copland
Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA.
Brigid
B
Bradley-Garelik
Create for Chloe and UK representative for aPODD, UK.
Debbie
D
Binner
Novartis Pharma AG, Basel CH-4002, Switzerland.
Renaud
R
Capdeville
Hoffman-La Roche, Basel, Switzerland; Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Hubert
H
Caron
Belgian Federal Agency for Medicines and Health Products, Brussels, Belgium.
Jacqueline
J
Carleer
Division of Clinical Studies, The Institute of Cancer Research, London, UK.
Louis
L
Chesler
Department of Pediatric and Adolescent Oncology, Gustave Roussy, France.
Birgit
B
Geoerger
Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Pamela
P
Kearns
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.
Lynley V
LV
Marshall
German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), and Heidelberg University Hospital, Heidelberg 69120, Germany.
Stefan M
SM
Pfister
U830 INSERM, Recherche Translationelle en Oncologie Pédiatrique (RTOP) and Department of Pediatric Oncology, Institut Curie, Paris, France.
Gudrun
G
Schleiermacher
TetraLogic Pharmaceuticals, Malvern, PA 19355, USA.
Jeffrey
J
Skolnik
aPODD Foundation, London, UK.
Cesare
C
Spadoni
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.
Jaroslav
J
Sterba
Product Development Scientific Support Department, European Medicines Agency, Canary Wharf, London, UK.
Hendrick
H
van den Berg
Boehringer Ingelheim, Germany.
Martina
M
Uttenreuther-Fischer
Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Olaf
O
Witt
Paediatric Haematology/Oncology Unit, Antwerp University Hospital, Antwerp University, Belgium.
Koen
K
Norga
Department of Clinical Research, Institut Gustave Roussy, Paris-Sud University, Paris, France.
Gilles
G
Vassal
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D004341:Drug Evaluation; D004345:Drug Industry / Q000379:methods; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents
Mechanism of action; Paediatric oncology; Targeted cancer drug development