title: MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children.
abstract: BACKGROUND
  Primary melanoma of the CNS in children is extremely rare, and usually linked to congenital melanocytic naevus syndrome, caused by mosaicism for oncogenic NRAS mutations. Outcome is fatal in all cases. Data from murine and in vitro studies suggest that MEK inhibition is a possible therapeutic option.
  
  
  METHODS
  Four children with NRAS-mutated CNS melanoma were treated with Trametinib on a compassionate basis.
  
  
  RESULTS
  All four had an improvement in symptoms and objectively in signs. These varied from mild improvement for 1 month, to a sustained symptom-free period of 9 months in one case. In all cases there was eventual disease progression through treatment, followed by rapid death after discontinuation. There were no clinically-significant side effects.
  
  
  CONCLUSIONS
  Trametinib is the first therapy to show any objective or measurable effect in NRAS-mutated primary CNS melanoma, with few side effects in this small series. The role of this therapy should be explored further in this rare paediatric tumour.
authors.affiliation: Paediatric Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.|Genetics and Genomic Medicine, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Kinsler
authors.affiliation: Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: O'Hare
authors.affiliation: Paediatric Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacques
authors.affiliation: Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.|Developmental Biology and Cancer Programme, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Hargrave
authors.affiliation: Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
authors.forename: Olga
authors.initials: O
authors.lastname: Slater
mesh_terms: D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D007223:Infant; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human