Theranostics
2017; 7(3):717-732.
doi:10.7150/thno.17154 This issueCite
Research Paper
HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors
Olga Martinho1,2,3✉, Renato Silva-Oliveira3, Fernanda P. Cury3, Ana Martins Barbosa1,2, Sara Granja1,2, Adriane Feijó Evangelista3, Fábio Marques4, Vera Miranda-Gonçalves1,2, Diana Cardoso-Carneiro1,2, Flávia E. de Paula3, Maicon Zanon3, Cristovam Scapulatempo-Neto3, Marise A.R. Moreira4, Fátima Baltazar1,2, Adhemar Longatto-Filho1,2,3,5, Rui Manuel Reis1,2,3✉
1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; 2. ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal; 3. Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil; 4. Department of Pathology of the School of Medicine of the Federal University of Goiás, Brazil; 5. Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, São Paulo State University, Brazil.
✉ Corresponding authors: Olga Martinho, PhD. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Phone: + 351 253 604868 E-mail: olgamartinho@med.uminho.pt AND Rui Manuel Reis, PhD. Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, CEP 14784-400, Barretos, S. Paulo, Brazil. E-mail: ruireis.hcb@gmail.com.More
Citation:
Martinho O, Silva-Oliveira R, Cury FP, Barbosa AM, Granja S, Evangelista AF, Marques F, Miranda-Gonçalves V, Cardoso-Carneiro D, de Paula FE, Zanon M, Scapulatempo-Neto C, Moreira MAR, Baltazar F, Longatto-Filho A, Reis RM. HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics 2017; 7(3):717-732. doi:10.7150/thno.17154. https://www.thno.org/v07p0717.htm
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-α-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.
Martinho, O., Silva-Oliveira, R., Cury, F.P., Barbosa, A.M., Granja, S., Evangelista, A.F., Marques, F., Miranda-Gonçalves, V., Cardoso-Carneiro, D., de Paula, F.E., Zanon, M., Scapulatempo-Neto, C., Moreira, M.A.R., Baltazar, F., Longatto-Filho, A., Reis, R.M. (2017). HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics, 7(3), 717-732. https://doi.org/10.7150/thno.17154.
ACS
Martinho, O.; Silva-Oliveira, R.; Cury, F.P.; Barbosa, A.M.; Granja, S.; Evangelista, A.F.; Marques, F.; Miranda-Gonçalves, V.; Cardoso-Carneiro, D.; de Paula, F.E.; Zanon, M.; Scapulatempo-Neto, C.; Moreira, M.A.R.; Baltazar, F.; Longatto-Filho, A.; Reis, R.M. HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics 2017, 7 (3), 717-732. DOI: 10.7150/thno.17154.
NLM
Martinho O, Silva-Oliveira R, Cury FP, Barbosa AM, Granja S, Evangelista AF, Marques F, Miranda-Gonçalves V, Cardoso-Carneiro D, de Paula FE, Zanon M, Scapulatempo-Neto C, Moreira MAR, Baltazar F, Longatto-Filho A, Reis RM. HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics 2017; 7(3):717-732. doi:10.7150/thno.17154. https://www.thno.org/v07p0717.htm
CSE
Martinho O, Silva-Oliveira R, Cury FP, Barbosa AM, Granja S, Evangelista AF, Marques F, Miranda-Gonçalves V, Cardoso-Carneiro D, de Paula FE, Zanon M, Scapulatempo-Neto C, Moreira MAR, Baltazar F, Longatto-Filho A, Reis RM. 2017. HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors. Theranostics. 7(3):717-732.