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

Background We 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) block...

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Bibliographic Details
Published in:Head & neck 2023-07, Vol.45 (7), p.1801-1811
Main Authors: Aoyama, Jun, Nojima, Yusuke, Sano, Daisuke, Hirai, Yuri, Kijima, Natsumi, Aizawa, Yoshihiro, Takada, Kentaro, Hatano, Takashi, Takahashi, Hideaki, Nishimura, Goshi, Oridate, Nobuhiko
Format: Article
Language:English
Subjects:
Apoptosis
Carcinoma
Cell proliferation
ErbB-2 protein
HER2
lapatinib
Oral cancer
Organoids
patient‐derived organoid
Phosphorylation
salivary duct carcinoma
salivary gland cancer
siRNA
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Summary:Background We 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. Methods The 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. Results The 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. Conclusion For the first time, we demonstrated the efficacy of anti‐HER2 therapy in HER2‐positive SDC using preclinical models of SDC PDX and PDXO.
ISSN:1043-3074
1097-0347
DOI:10.1002/hed.27395