Theranostics 2017; 7(3):717-732. doi:10.7150/thno.17154

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.

Abstract

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.

Keywords: ErbB, EGFR, HER2, cervical cancer, prognosis, targeted therapy.

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How to cite this article:
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. Available from http://www.thno.org/v07p0717.htm