HER2 as a novel therapeutic target for cervical cancer.
HER2 as a novel therapeutic target for cervical cancer.
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DOI：
10.18632/oncotarget.5283
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发表时间：
2015-11-03
期刊：
影响因子：
--
通讯作者：
Song S
中科院分区：
文献类型：
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作者：
Oh DY;Kim S;Choi YL;Cho YJ;Oh E;Choi JJ;Jung K;Song JY;Ahn SE;Kim BG;Bae DS;Park WY;Lee JW;Song S
手术和放疗是目前宫颈癌的标准治疗方法。然而，对于转移性或复发性病例没有有效的治疗方法，需要确定治疗靶点。为了建立筛选潜在治疗靶点的临床前模型，我们使用肾下植入方法建立了14个宫颈癌患者来源的异种移植（PDX）模型。连续传代的PDX肿瘤保留了原始肿瘤的组织病理学和基因组特征。在9个分子特征的宫颈癌患者样本中，通过阵列比较基因组杂交和靶向下一代测序检测到HER2扩增肿瘤。我们证实了肿瘤中的HER2过表达，并连续传代PDX。与对照组相比，曲妥珠单抗和拉帕替尼在HER2过表达的PDX中的联合给药显著抑制了肿瘤生长。因此，我们建立了组织病理学和基因组同源PDX模型的宫颈癌肾下种植。此外，我们提出了基于HER2的疗法，用于常规疗法难治的HER2扩增的宫颈癌。
Surgery and radiation are the current standard treatments for cervical cancer. However, there is no effective therapy for metastatic or recurrent cases, necessitating the identification of therapeutic targets. In order to create preclinical models for screening potential therapeutic targets, we established 14 patient-derived xenograft (PDX) models of cervical cancers using subrenal implantation methods. Serially passaged PDX tumors retained the histopathologic and genomic features of the original tumors. Among the 9 molecularly profiled cervical cancer patient samples, a HER2-amplified tumor was detected by array comparative genomic hybridization and targeted next-generation sequencing. We confirmed HER2 overexpression in the tumor and serially passaged PDX. Co-administration of trastuzumab and lapatinib in the HER2-overexpressed PDX significantly inhibited tumor growth compared to the control. Thus, we established histopathologically and genomically homologous PDX models of cervical cancer using subrenal implantation. Furthermore, we propose HER2 inhibitor-based therapy for HER2-amplified cervical cancer refractory to conventional therapy.