HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.7150/thno.17154 http://hdl.handle.net/11449/159432 |
Resumo: | Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-a-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients. |
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HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER InhibitorsErbBEGFRHER2cervical cancerprognosistargeted therapyPersistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-a-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.FINEP, Brazilproject ON.2 SR&-TD Integrated Program - Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER)Fundacao para a Ciencia e Tecnologia (FCT), PortugalFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, PortugalPT Govt Associate Lab, ICVS Bs3, Braga, PortugalBarretos Canc Hosp, Mol Oncol Res Ctr CPOM, Sao Paulo, BrazilUniv Fed Goias, Sch Med, Dept Pathol, Goiania, Go, BrazilSao Paulo State Univ, Fac Med, Lab Med Invest LIM 14, Sao Paulo, BrazilSao Paulo State Univ, Fac Med, Lab Med Invest LIM 14, Sao Paulo, BrazilFINEP, Brazil: 1302/13project ON.2 SR&-TD Integrated Program - Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER): NORTE-07-0124-FEDER-000017Fundacao para a Ciencia e Tecnologia (FCT), Portugal: SFRH/BPD/108351/2015Fundacao para a Ciencia e Tecnologia (FCT), Portugal: SFRH/BD/51997/2012FAPESP: 2014/03684-0Ivyspring Int PublUniv MinhoPT Govt Associate LabBarretos Canc HospUniversidade Federal de Goiás (UFG)Universidade Estadual Paulista (Unesp)Martinho, OlgaSilva-Oliveira, RenatoCury, Fernanda P.Barbosa, Ana MartinsGranja, SaraEvangelista, Adriane FeijoMarques, FabioMiranda-Goncalves, VeraCardoso-Carneiro, DianaPaula, Flavia E. deZanon, MaiconScapulatempo-Neto, CristovamMoreira, Marise A. R.Baltazar, FatimaLongatto-Filho, AdhemarReis, Rui Manuel2018-11-26T15:43:45Z2018-11-26T15:43:45Z2017-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article717-732application/pdfhttp://dx.doi.org/10.7150/thno.17154Theranostics. Lake Haven: Ivyspring Int Publ, v. 7, n. 3, p. 717-732, 2017.1838-7640http://hdl.handle.net/11449/15943210.7150/thno.17154WOS:000396557300017Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengTheranostics2,515info:eu-repo/semantics/openAccess2023-10-02T06:04:53Zoai:repositorio.unesp.br:11449/159432Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:45:53.560445Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
title |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
spellingShingle |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors Martinho, Olga ErbB EGFR HER2 cervical cancer prognosis targeted therapy |
title_short |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
title_full |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
title_fullStr |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
title_full_unstemmed |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
title_sort |
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors |
author |
Martinho, Olga |
author_facet |
Martinho, Olga Silva-Oliveira, Renato Cury, Fernanda P. Barbosa, Ana Martins Granja, Sara Evangelista, Adriane Feijo Marques, Fabio Miranda-Goncalves, Vera Cardoso-Carneiro, Diana Paula, Flavia E. de Zanon, Maicon Scapulatempo-Neto, Cristovam Moreira, Marise A. R. Baltazar, Fatima Longatto-Filho, Adhemar Reis, Rui Manuel |
author_role |
author |
author2 |
Silva-Oliveira, Renato Cury, Fernanda P. Barbosa, Ana Martins Granja, Sara Evangelista, Adriane Feijo Marques, Fabio Miranda-Goncalves, Vera Cardoso-Carneiro, Diana Paula, Flavia E. de Zanon, Maicon Scapulatempo-Neto, Cristovam Moreira, Marise A. R. Baltazar, Fatima Longatto-Filho, Adhemar Reis, Rui Manuel |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Minho PT Govt Associate Lab Barretos Canc Hosp Universidade Federal de Goiás (UFG) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Martinho, Olga Silva-Oliveira, Renato Cury, Fernanda P. Barbosa, Ana Martins Granja, Sara Evangelista, Adriane Feijo Marques, Fabio Miranda-Goncalves, Vera Cardoso-Carneiro, Diana Paula, Flavia E. de Zanon, Maicon Scapulatempo-Neto, Cristovam Moreira, Marise A. R. Baltazar, Fatima Longatto-Filho, Adhemar Reis, Rui Manuel |
dc.subject.por.fl_str_mv |
ErbB EGFR HER2 cervical cancer prognosis targeted therapy |
topic |
ErbB EGFR HER2 cervical cancer prognosis targeted therapy |
description |
Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-a-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 2018-11-26T15:43:45Z 2018-11-26T15:43:45Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.7150/thno.17154 Theranostics. Lake Haven: Ivyspring Int Publ, v. 7, n. 3, p. 717-732, 2017. 1838-7640 http://hdl.handle.net/11449/159432 10.7150/thno.17154 WOS:000396557300017 |
url |
http://dx.doi.org/10.7150/thno.17154 http://hdl.handle.net/11449/159432 |
identifier_str_mv |
Theranostics. Lake Haven: Ivyspring Int Publ, v. 7, n. 3, p. 717-732, 2017. 1838-7640 10.7150/thno.17154 WOS:000396557300017 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Theranostics 2,515 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
717-732 application/pdf |
dc.publisher.none.fl_str_mv |
Ivyspring Int Publ |
publisher.none.fl_str_mv |
Ivyspring Int Publ |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128274216255488 |