Laser-assisted topical delivery of vismodegib reduces hedgehog gene expression in human basal cell carcinomas in vivo.
ablative fractional laser
basal cell carcinoma
clinical trial
emulsion drug formulation
laser-assisted drug delivery
vismodegib
Journal
Lasers in surgery and medicine
ISSN: 1096-9101
Titre abrégé: Lasers Surg Med
Pays: United States
ID NLM: 8007168
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
revised:
19
01
2024
received:
14
12
2023
accepted:
22
01
2024
pubmed:
5
2
2024
medline:
5
2
2024
entrez:
5
2
2024
Statut:
ppublish
Résumé
Systemically delivered hedgehog inhibitors including vismodegib and sonidegib are widely used to treat basal cell carcinomas (BCCs). Ablative fractional laser (AFL)-assisted topical delivery of vismodegib has been demonstrated in preclinical studies. The aim of this explorative clinical study was to evaluate intratumoral vismodegib concentrations and effect on hedgehog pathway gene expression following AFL-assisted topical vismodegib delivery to BCCs. In an open-label clinical trial, 16 nodular BCCs (in n = 9 patients) received one application of CO Following AFL-assisted topical administration, vismodegib was detected in 14/15 BCCs and reached a median concentration of 6.2 µmol/L, which compared to concentrations in BCC tissue from patients receiving oral vismodegib (9.5 µmol/L, n = 3, p = 0.8588). Topical vismodegib reduced intratumoral GLI1 expression by 51%, GLI2 by 55%, PTCH1 and PTCH2 each by 73% (p ≤ 0.0304) regardless of vismodegib concentrations (p ≥ 0.3164). In situ hybridization demonstrated that GLI1 expression was restricted to tumor tissue and downregulated in response to vismodegib exposure. A single AFL-assisted topical application of vismodegib resulted in clinically relevant intratumoral drug concentrations and significant reductions in hedgehog pathway gene expressions.
Sections du résumé
BACKGROUND
BACKGROUND
Systemically delivered hedgehog inhibitors including vismodegib and sonidegib are widely used to treat basal cell carcinomas (BCCs). Ablative fractional laser (AFL)-assisted topical delivery of vismodegib has been demonstrated in preclinical studies. The aim of this explorative clinical study was to evaluate intratumoral vismodegib concentrations and effect on hedgehog pathway gene expression following AFL-assisted topical vismodegib delivery to BCCs.
METHODS
METHODS
In an open-label clinical trial, 16 nodular BCCs (in n = 9 patients) received one application of CO
RESULTS
RESULTS
Following AFL-assisted topical administration, vismodegib was detected in 14/15 BCCs and reached a median concentration of 6.2 µmol/L, which compared to concentrations in BCC tissue from patients receiving oral vismodegib (9.5 µmol/L, n = 3, p = 0.8588). Topical vismodegib reduced intratumoral GLI1 expression by 51%, GLI2 by 55%, PTCH1 and PTCH2 each by 73% (p ≤ 0.0304) regardless of vismodegib concentrations (p ≥ 0.3164). In situ hybridization demonstrated that GLI1 expression was restricted to tumor tissue and downregulated in response to vismodegib exposure.
CONCLUSION
CONCLUSIONS
A single AFL-assisted topical application of vismodegib resulted in clinically relevant intratumoral drug concentrations and significant reductions in hedgehog pathway gene expressions.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
239-248Informations de copyright
© 2024 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.
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