title: HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors.
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 usingin vitroandin vivoapproaches, 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.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal;; Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Olga
authors.initials: O
authors.lastname: Martinho
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Renato
authors.initials: R
authors.lastname: Silva-Oliveira
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Cury
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Ana Martins
authors.initials: AM
authors.lastname: Barbosa
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Adriane Feijó
authors.initials: AF
authors.lastname: Evangelista
authors.affiliation: Department of Pathology of the School of Medicine of the Federal University of Goiás, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Marques
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Miranda-Gonçalves
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Cardoso-Carneiro
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Flávia E
authors.initials: FE
authors.lastname: de Paula
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Maicon
authors.initials: M
authors.lastname: Zanon
authors.affiliation: Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: Department of Pathology of the School of Medicine of the Federal University of Goiás, Brazil.
authors.forename: Marise A R
authors.initials: MA
authors.lastname: Moreira
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal;; Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil;; Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, São Paulo State University, Brazil.
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal;; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal;; Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000178:Acrylamides / Q000627:therapeutic use; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy*; D000963:Antimetabolites / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000037:antagonists & inhibitors; D003955:Diagnostic Tests, Routine / Q000379:methods; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis* / Q000037:antagonists & inhibitors*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines / Q000627:therapeutic use; D000068936:Theranostic Nanomedicine / Q000379:methods; D045506:Therapeutic Uses; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: C568037:AST 1306; D000178:Acrylamides; D000963:Antimetabolites; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D045506:Therapeutic Uses; D000077341:Lapatinib; D066246:ErbB Receptors; D005947:Glucose
keywords: EGFR; ErbB; HER2; cervical cancer; prognosis; targeted therapy.