Erschienen in:
12.11.2019 | Original Article
First insights for targeted therapies in odontogenic myxoma
verfasst von:
Núbia Braga Pereira, Victor Coutinho Bastos, Juliana Cristina de Souza, Marina Gonçalves Diniz, Jéssica Gardone Vitório, Gregory Thomas Kitten, Luciana de Oliveira Andrade, Gleide Fernandes de Avelar, Wagner Henriques Castro, Vanessa Fátima Bernardes, Adriana Abalen Martins Dias, Ricardo Santiago Gomez, Carolina Cavalieri Gomes
Erschienen in:
Clinical Oral Investigations
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Ausgabe 7/2020
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Abstract
Objective
Odontogenic myxoma (OM) occasionally responds poorly to surgical treatment. The MAPK pathway is constitutively activated in several neoplasms and we aimed to test if the MAPK pathway is activated in OM, in order to pave the way for an alternative therapy for aggressive and recurrent cases.
Materials and methods
The immunoexpression of phosphorylated ERK1/2 (pERK1/2) was assessed in OM. We established a 3D organotypic culture model for the in vitro study and patient-derived xenografts (PDX) in mice for the in vivo study. The MEK inhibitor U0126 was used to inhibit phosphorylation of ERK1/2 in the in vitro and in vivo models.
Results
All OM showed strong pERK1/2 immunoexpression, consistent with MAPK pathway activation. Treatment of the 3D culture with U0126 resulted in a reduced pERK1/2/ERK1/2 ratio. Consistent with the in vitro results, all PDX of animals treated with U0126 showed a decreased volume fold change compared with controls.
Conclusions
The MAPK pathway is activated in OM and its inhibition leads to tumor shrinkage in PDX and cell culture models.
Clinical relevance
Our results offer a pre-clinical frame for OM-targeted therapy. Further work is needed to determine if this initial finding holds clinical promise.