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Published on: July 25, 2020
First insights for targeted therapies in odontogenic myxoma
Núbia Braga Pereira1, Victor Coutinho Bastos1, Juliana Cristina de Souza1
1Department of Pathology, Biological Science Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Presidente Antônio Carlos, 6627 Pampulha, Belo Horizonte, Brazil.
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.
Insights
The MAPK pathway is activated in odontogenic myxoma (OM). Inhibiting this pathway with U0126 reduced tumor growth in cell cultures and animal models, suggesting a potential new therapy for aggressive OM.
Area of Science:
- Oncology
- Molecular Biology
- Oral Pathology
Background:
- Odontogenic myxoma (OM) can be challenging to treat surgically.
- The MAPK pathway is implicated in various cancers.
- Investigating the MAPK pathway in OM may reveal new therapeutic targets.
Purpose of the Study:
- To determine if the MAPK pathway is activated in OM.
- To explore the potential of targeting the MAPK pathway for OM treatment.
Main Methods:
- Assessed phosphorylated ERK1/2 (pERK1/2) immunoexpression in OM.
- Utilized 3D organotypic culture and patient-derived xenografts (PDX) in mice.
- Inhibited the MAPK pathway using the MEK inhibitor U0126.
Main Results:
- OM tissues exhibited strong pERK1/2 immunoexpression, indicating MAPK pathway activation.
- U0126 treatment reduced the pERK1/2/ERK1/2 ratio in 3D cultures.
- U0126 treatment significantly decreased tumor volume in PDX models.
Conclusions:
- The MAPK pathway is activated in OM.
- Inhibition of the MAPK pathway demonstrated anti-tumor effects in preclinical models.
- These findings provide a basis for developing targeted therapies for OM.
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