title: Targeted approaches to childhood cancer: progress in drug discovery and development.
abstract: BACKGROUND
  Cancer is a leading cause of death in childhood. Encouraging progress has been made in the treatment of childhood malignancies, but there is an unmet need for new drugs to improve survival and reduce treatment-associated toxicities. Drug development in paediatric oncology has specific requirements with regard to the patient population and the regulatory background and presents several unique challenges that need addressing.
  
  
  METHODS
  This review discusses the current framework of paediatric oncology drug development and some of the specific challenges in pre-clinical and clinical research. The authors discuss the recent developments in the targeting of various signalling pathways. These pathways represent a selection of targets that have been identified by pre-clinical and clinical investigators to be highly relevant in paediatric malignancies.
  
  
  CONCLUSIONS
  The development of targeted agents in paediatric oncology must be driven by knowledge of tumour biology. Predictive and pharmacodynamic biomarkers should be incorporated within paediatric early clinical trials wherever possible. Faster dose-escalation, limited numbers of cohorts and novel adaptive designs can help to make paediatric early clinical trials more efficient. Close collaboration between academic/clinical researchers, the pharmaceutical industry, regulatory bodies and parent groups are crucial in overcoming the challenges associated with paediatric oncology drug development.
authors.affiliation: The Royal Marsden NHS Foundation Trust, Children and Young People's Unit , Sutton, Surrey, SM2 5PT , UK +44 0 20 8915 6161 ; lucas.moreno@icr.ac.uk.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hirsch
authors.forename: Lynley V
authors.initials: LV
authors.lastname: Marshall
authors.forename: Fernando
authors.initials: F
authors.lastname: Carceller Lechon
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.forename: Lucas
authors.initials: L
authors.lastname: Moreno
mesh_terms: D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: drug development; oncology; paediatric; targeted therapy