Targeted treatment in complex lymphatic anomaly: a case of synergistic efficacy of trametinib and sirolimus.
Complex lymphatic anomaly
Infection
Lymphedema
Sirolimus
Trametinib
VASE
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
16 May 2024
16 May 2024
Historique:
received:
20
04
2024
accepted:
05
05
2024
medline:
16
5
2024
pubmed:
16
5
2024
entrez:
15
5
2024
Statut:
epublish
Résumé
Repurposing anticancer drugs to vascular malformations has significantly improved patient outcomes. Complex Lymphatic Anomalies (CLA) are part of the spectrum of lymphatic malformations (LMs) that share similar oncogenic mutations to cancer. We report the case of a young patient with highly symptomatic CLA who was initially treated with sirolimus, due to the frequent involvement of the PI3K-AKT-mTOR pathway in CLA pathogenesis. Despite an initial reduction in symptoms, sirolimus progressively lost its effectiveness. After an unsuccessful attempt with trametinib alone, sirolimus was added to trametinib and resulted in a significant, rapid and sustained improvement in symptoms. This suggests that, contrary to current dogmas, combination therapy using sub-therapeutic doses targeting both the PI3K and RAS pathways retains efficacy without generating the toxicity known for combination therapies, and is beneficial in the management of CLAs and potentially other vascular anomalies.
Identifiants
pubmed: 38750525
doi: 10.1186/s13023-024-03211-z
pii: 10.1186/s13023-024-03211-z
doi:
Types de publication
Case Reports
Letter
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
199Informations de copyright
© 2024. The Author(s).
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