Effect of HER2-targeted therapy on PDX and PDX-derived organoids generated from HER2-positive salivary duct carcinoma

被引：2
|
作者：
Aoyama, Jun [1 ]
Nojima, Yusuke [1 ]
Sano, Daisuke [1 ,2 ,3 ]
Hirai, Yuri [1 ]
Kijima, Natsumi [1 ]
Aizawa, Yoshihiro [1 ]
Takada, Kentaro [1 ]
Hatano, Takashi [1 ]
Takahashi, Hideaki [1 ]
Nishimura, Goshi [1 ]
Oridate, Nobuhiko [1 ,2 ]
机构：
[1] Yokohama City Univ, Grad Sch Med, Dept Biol & Funct Head & Neck, Yokohama, Japan
[2] Yokohama City Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Yokohama, Japan
[3] Yokohama City Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, 3-9 Fukuura,Kanazawa Ku, Yokohama 2360004, Japan
来源：
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK | 2023年 / 45卷 / 07期
基金：
日本学术振兴会;
关键词：
HER2; lapatinib; patient-derived organoid; salivary duct carcinoma; salivary gland cancer; FACTOR RECEPTOR EGFR; LAPATINIB; BREAST; TRASTUZUMAB; RESISTANCE; INHIBITOR; GW572016; HEAD;
D O I：
10.1002/hed.27395
中图分类号：
R76 [耳鼻咽喉科学];
学科分类号：
100213 ;
摘要：
BackgroundWe previously established a patient-derived xenograft (PDX) model, patient-derived organoids (PDOs), and PDX-derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2-positive SDC. MethodsThe therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. ResultsThe siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. ConclusionFor the first time, we demonstrated the efficacy of anti-HER2 therapy in HER2-positive SDC using preclinical models of SDC PDX and PDXO.
引用
收藏
页码：1801 / 1811
页数：11
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