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01-07-2020 | Targeted Therapy | Original Article

First insights for targeted therapies in odontogenic myxoma

Authors: 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

Published in: Clinical Oral Investigations | Issue 7/2020

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.

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Title: First insights for targeted therapies in odontogenic myxoma
Authors: 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
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keyword: Targeted Therapy
Published in: Clinical Oral Investigations / Issue 7/2020
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-019-03107-4

At a glance: The STEP trials

Springer Medicine

First insights for targeted therapies in odontogenic myxoma

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

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