Martinho Olga, Silva-Oliveira Renato, Cury Fernanda P, Barbosa Ana Martins, Granja Sara, Evangelista Adriane Feijó, Marques Fábio, Miranda-Gonçalves Vera, Cardoso-Carneiro Diana, de Paula Flávia E, Zanon Maicon, Scapulatempo-Neto Cristovam, Moreira Marise A R, Baltazar Fátima, Longatto-Filho Adhemar, Reis Rui Manuel
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.
Molecular Oncology Research Center (CPOM), Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Theranostics. 2017 Jan 15;7(3):717-732. doi: 10.7150/thno.17154. eCollection 2017.
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 and 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.
单纯持续性人乳头瘤病毒(HPV)感染不足以引发宫颈癌,宫颈癌的发展还需要其他分子改变,以促进肿瘤进展和转移,最终导致致命疾病。在本研究中,我们对宫颈腺癌中HER家族受体改变进行了全面分析。我们检测到HER蛋白,主要是HER2的过表达,这是这些患者的独立预后标志物。通过使用[具体方法1]和[具体方法2]方法,我们证明了HER抑制剂阿来替尼和拉帕替尼在降低宫颈癌侵袭性方面是有效的。此外,这些药物与葡萄糖摄取阻滞剂联合使用可以克服假定的HIF1-α介导的对HER靶向治疗的耐药性。因此,我们提出,HER抑制剂与糖酵解阻滞剂联合使用可能是HER阳性宫颈癌患者的一种潜在有效治疗选择。