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Tyrosine kinase inhibitors are promising therapeutic tools for cats with HER2-positive mammary carcinoma

2021-03-06Journal article Open access
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dc.contributor.authorGameiro, Andreia
dc.contributor.authorAlmeida, Filipe
dc.contributor.authorNascimento, Catarina
dc.contributor.authorCorreia, Jorge Manuel de Jesus
dc.contributor.authorFerreira, Fernando
dc.date.accessioned2022-02-05T23:54:15Z
dc.date.available2022-02-05T23:54:15Z
dc.date.issued2021-03-06
dc.descriptionResearch Areas: Pharmacology & Pharmacypt_PT
dc.description.abstractABSTRACT - Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman’s breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGameiro A, Almeida F, Nascimento C, Correia J, Ferreira F. 2021. Tyrosine kinase inhibitors are promising therapeutic tools for cats with HER2-positive mammary carcinoma. Pharmaceutics, 13(3):346. Doi: 10.3390/pharmaceutics13030346pt_PT
dc.identifier.doi10.3390/pharmaceutics13030346pt_PT
dc.identifier.eissn1999-4923
dc.identifier.urihttp://hdl.handle.net/10400.5/23406
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationC00191rpt_PT
dc.relationCentre for Interdisciplinary Research in Animal Health
dc.relationDeveloping diagnostic tools for feline mammary carcinomas and improving chemotherapy based on HER2 and topoisometase status
dc.relation.publisherversionhttps://www.mdpi.com/1999-4923/13/3/346pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectFeline mammary carcinomapt_PT
dc.subjectHER2pt_PT
dc.subjectTyrosine kinase inhibitorspt_PT
dc.subjectTargeted therapiespt_PT
dc.subjectFeline her2 TK mutationspt_PT
dc.titleTyrosine kinase inhibitors are promising therapeutic tools for cats with HER2-positive mammary carcinomapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Interdisciplinary Research in Animal Health
oaire.awardTitleDeveloping diagnostic tools for feline mammary carcinomas and improving chemotherapy based on HER2 and topoisometase status
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCVT-EPI%2F3638%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00276%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F132260%2F2017/PT
oaire.citation.conferencePlaceBasel, Switzerlandpt_PT
oaire.citation.titlePharmaceuticspt_PT
oaire.citation.volumeVol.13(3):346pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGameiro
person.familyNameGaspar do Nascimento
person.familyNameJesus Correia
person.familyNameFerreira
person.givenNameAndreia
person.givenNameAna Catarina
person.givenNameJorge Manuel
person.givenNameFernando António da Costa
person.identifier.ciencia-idB718-5199-AA36
person.identifier.ciencia-id7311-54F2-A545
person.identifier.ciencia-idF81F-D7D4-57C5
person.identifier.orcid0000-0002-1602-3552
person.identifier.orcid0000-0002-1909-4540
person.identifier.orcid0000-0001-5765-576X
person.identifier.scopus-author-id7202364133
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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