First insights for targeted therapies in odontogenic myxoma

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dc.creatorNúbia Braga Pereira
dc.creatorVanessa Fátima Bernardes
dc.creatorAdriana Abalen Martins Dias
dc.creatorRicardo Santiago Gomez
dc.creatorCarolina Cavalieri Gomes
dc.creatorVictor Coutinho Bastos
dc.creatorJuliana Cristina de Souza
dc.creatorMarina Gonçalves Diniz
dc.creatorJéssica Gardone Vitório
dc.creatorGregory Thomas Kitten
dc.creatorLuciana de Oliveira Andrade
dc.creatorGleide Fernandes de Avelar
dc.creatorWagner Henriques de Castro
dc.date.accessioned2025-05-29T19:10:38Z
dc.date.accessioned2025-09-09T01:20:24Z
dc.date.available2025-05-29T19:10:38Z
dc.date.issued2020-07
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1007/s00784-019-03107-4
dc.identifier.issn1436-3771
dc.identifier.urihttps://hdl.handle.net/1843/82633
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofClinical Oral Investigations
dc.rightsAcesso Restrito
dc.subjectCell culture techniques, three dimensional
dc.subjectMitogen-activated protein kinase kinases
dc.subjectExtracellular signal-regulated MAP kinases
dc.subjectMAP kinase signaling system
dc.subjectMAP kinase kinase kinases
dc.subjectOdontogenic tumors
dc.subjectHeterografts
dc.subjectTherapeutics
dc.subject.other3D cell culture
dc.subject.otherERK
dc.subject.otherMAPK pathway
dc.subject.otherMEK inhibition
dc.subject.otherOdontogenic tumors
dc.subject.otherPDX
dc.subject.otherTargeted therapy
dc.titleFirst insights for targeted therapies in odontogenic myxoma
dc.typeArtigo de periódico
local.citation.epage2458
local.citation.issue7
local.citation.spage2451
local.citation.volume24
local.description.resumoObjective: 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.
local.identifier.orcidhttps://orcid.org/0000-0002-6714-3124
local.identifier.orcidhttps://orcid.org/0000-0003-0194-7434
local.identifier.orcidhttps://orcid.org/0000-0001-9415-3240
local.identifier.orcidhttps://orcid.org/0000-0001-8770-8009
local.identifier.orcidhttps://orcid.org/0000-0003-1580-4995
local.identifier.orcidhttps://orcid.org/0000-0003-0360-4179
local.identifier.orcidhttps://orcid.org/0000-0002-4212-1172
local.identifier.orcidhttps://orcid.org/0000-0002-5009-6675
local.identifier.orcidhttps://orcid.org/0000-0002-4044-9932
local.identifier.orcidhttps://orcid.org/0000-0002-2132-3218
local.identifier.orcidhttps://orcid.org/0000-0003-2745-2878
local.publisher.countryBrasil
local.publisher.departmentFAO - DEPARTAMENTO DE CLÍNICA
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE PATOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://link.springer.com/article/10.1007/s00784-019-03107-4

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