PMID- 28253523
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20181113
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 116
IP  - 8
DP  - 2017 Apr 11
TI  - MEK inhibition appears to improve symptom control in primary NRAS-driven CNS
      melanoma in children.
PG  - 990-993
LID - 10.1038/bjc.2017.49 [doi]
AB  - 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.
FAU - Kinsler, Veronica A
AU  - Kinsler VA
AD  - Paediatric Dermatology, Great Ormond Street Hospital for Children NHS Foundation 
      Trust, London WC1N 3JH, UK.
AD  - Genetics and Genomic Medicine, UCL Institute of Child Health, 30 Guilford Street,
      London WC1N 1EH, UK.
FAU - O'Hare, Patricia
AU  - O'Hare P
AD  - Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation
      Trust, London WC1N 3JH, UK.
FAU - Jacques, Thomas
AU  - Jacques T
AD  - Paediatric Histopathology, Great Ormond Street Hospital for Children NHS
      Foundation Trust, London WC1N 3JH, UK.
FAU - Hargrave, Darren
AU  - Hargrave D
AD  - Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation
      Trust, London WC1N 3JH, UK.
AD  - Developmental Biology and Cancer Programme, UCL Institute of Child Health, 30
      Guilford Street, London WC1N 1EH, UK.
FAU - Slater, Olga
AU  - Slater O
AD  - Paediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation
      Trust, London WC1N 3JH, UK.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20170302
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Membrane Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidinones)
RN  - 33E86K87QN (trametinib)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (NRAS protein, human)
SB  - IM
MH  - Central Nervous System Neoplasms/*drug therapy/genetics/pathology
MH  - Child, Preschool
MH  - Female
MH  - GTP Phosphohydrolases/*genetics
MH  - Humans
MH  - Infant
MH  - MAP Kinase Kinase 1/*antagonists & inhibitors
MH  - Male
MH  - Melanoma/*drug therapy/genetics/pathology
MH  - Membrane Proteins/*genetics
MH  - Mutation/*genetics
MH  - Prognosis
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyridones/*therapeutic use
MH  - Pyrimidinones/*therapeutic use
MH  - Skin Neoplasms/*drug therapy/genetics/pathology
PMC - PMC5396107
EDAT- 2017/03/03 06:00
MHDA- 2017/06/07 06:00
CRDT- 2017/03/03 06:00
PHST- 2016/10/12 00:00 [received]
PHST- 2016/12/11 00:00 [revised]
PHST- 2017/01/20 00:00 [accepted]
PHST- 2017/03/03 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2017/03/03 06:00 [entrez]
AID - bjc201749 [pii]
AID - 10.1038/bjc.2017.49 [doi]
PST - ppublish
SO  - Br J Cancer. 2017 Apr 11;116(8):990-993. doi: 10.1038/bjc.2017.49. Epub 2017 Mar 
      2.