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Updated: Mar 6, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
MEK inhibition appears to improve symptom control in primary NRAS-driven CNS melanoma in children
Veronica A Kinsler1,2, Patricia O'Hare3, Thomas Jacques4
1Paediatric Dermatology, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
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.
Insights
Trametinib shows promise for treating rare pediatric brain melanoma. This MEK inhibitor improved symptoms in children with NRAS-mutated tumors, offering a potential new therapy.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Molecular Oncology
Background:
- Primary central nervous system (CNS) melanoma in children is exceedingly rare and typically associated with congenital melanocytic nevus syndrome.
- These tumors are driven by mosaic NRAS mutations and have historically had a fatal outcome.
- Preclinical data suggest MEK inhibition as a potential therapeutic strategy.
Observation:
- Four pediatric patients with NRAS-mutated CNS melanoma received Trametinib under compassionate use.
- Treatment response varied, with some experiencing temporary symptom relief and objective sign improvement.
- One patient remained symptom-free for nine months.
Findings:
- Trametinib demonstrated the first objective and measurable therapeutic effect in this rare pediatric CNS malignancy.
- All patients eventually experienced disease progression despite treatment.
- No significant side effects were observed during the treatment period.
Implications:
- Trametinib represents a potential first-line therapy for NRAS-mutated pediatric CNS melanoma.
- Further investigation into Trametinib's role in treating this rare pediatric tumor is warranted.
- This study highlights the importance of targeted therapy in pediatric neuro-oncology.
