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First insights for targeted therapies in odontogenic myxoma

  • 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 GomesEmail author
Original Article
  • 40 Downloads

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.

Keywords

Odontogenic tumors MEK inhibition Targeted therapy ERK MAPK pathway 3D cell culture PDX 

Notes

Author contributions

Núbia Braga Pereira: Original draft preparation, worked on the experiments and revision of the final version of the manuscript

Victor Coutinho Bastos: Worked on the experiments and revision of the final version of the manuscript

Juliana Cristina de Souza: Worked on the experiments and revision of the final version of the manuscript

Marina Gonçalves Diniz: Data analyses and revision of the final version of the manuscript

Jéssica Gardone Vitório: Worked on the experiments and revision of the final version of the manuscript

Gregory Thomas Kitten: Data analyses and revision of the final version of the manuscript

Luciana de Oliveira Andrade: Data analyses and revision of the final version of the manuscript

Gleide Fernandes de Avelar: Data analyses and revision of the final version of the manuscript

Wagner Henriques Castro: Data acquisition and revision of the final version of the manuscript

Vanessa Fátima Bernardes: Data analyses and revision of the final version of the manuscript

Adriana Abalen Martins Dias: Data analyses and revision of the final version of the manuscript

Ricardo Santiago Gomez: Data analyses and revision of the final version of the manuscript

Carolina Cavalieri Gomes: Supervision of the study, original draft preparation, data analyses, and revision of the final version of the manuscript

Funding information

This study was financed in part by the Coordination for the Improvement of Higher Education Personnel (CAPES)/Brazil, Finance code 001, the National Council for Scientific and Technological Development (CNPq)/Brazil, and the Research Support Foundation of the State of Minas Gerais (FAPEMIG)/Brazil. NBP receive CAPES scholarship. RSG and CCG are research fellows at CNPq.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the University Ethics Committee (Protocol CAAE 48121415.2.0000.5149) and by the University Ethics Committee on the Use of Animals (Protocol 201/2015). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Núbia Braga Pereira
    • 1
  • Victor Coutinho Bastos
    • 1
  • Juliana Cristina de Souza
    • 1
  • Marina Gonçalves Diniz
    • 1
  • Jéssica Gardone Vitório
    • 2
  • Gregory Thomas Kitten
    • 3
  • Luciana de Oliveira Andrade
    • 3
  • Gleide Fernandes de Avelar
    • 3
  • Wagner Henriques Castro
    • 2
  • Vanessa Fátima Bernardes
    • 1
  • Adriana Abalen Martins Dias
    • 4
  • Ricardo Santiago Gomez
    • 2
  • Carolina Cavalieri Gomes
    • 1
    Email author
  1. 1.Department of Pathology, Biological Science InstituteUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil
  2. 2.Department of Oral Surgery and Pathology, School of DentistryUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil
  3. 3.Department of Morphology, Biological Science InstituteUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil
  4. 4.Department of General Biology, Biological Science InstituteUniversidade Federal de Minas Gerais (UFMG)Belo HorizonteBrazil

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