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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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
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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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container_end_page 1811
container_issue 7
container_start_page 1801
container_title Head & neck
container_volume 45
creator Aoyama, Jun
Nojima, Yusuke
Sano, Daisuke
Hirai, Yuri
Kijima, Natsumi
Aizawa, Yoshihiro
Takada, Kentaro
Hatano, Takashi
Takahashi, Hideaki
Nishimura, Goshi
Oridate, Nobuhiko
description 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.
doi_str_mv 10.1002/hed.27395
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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.</description><identifier>ISSN: 1043-3074</identifier><identifier>EISSN: 1097-0347</identifier><identifier>DOI: 10.1002/hed.27395</identifier><identifier>PMID: 37184432</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>Apoptosis ; Carcinoma ; Cell proliferation ; ErbB-2 protein ; HER2 ; lapatinib ; Oral cancer ; Organoids ; patient‐derived organoid ; Phosphorylation ; salivary duct carcinoma ; salivary gland cancer ; siRNA</subject><ispartof>Head &amp; neck, 2023-07, Vol.45 (7), p.1801-1811</ispartof><rights>2023 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4345-9e0caee27fcf670c9ec22e20a60ed2714a89f47d60f8c2776d1a2f11703b5f473</cites><orcidid>0000-0003-3783-9961 ; 0000-0002-7686-4724</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37184432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aoyama, Jun</creatorcontrib><creatorcontrib>Nojima, Yusuke</creatorcontrib><creatorcontrib>Sano, Daisuke</creatorcontrib><creatorcontrib>Hirai, Yuri</creatorcontrib><creatorcontrib>Kijima, Natsumi</creatorcontrib><creatorcontrib>Aizawa, Yoshihiro</creatorcontrib><creatorcontrib>Takada, Kentaro</creatorcontrib><creatorcontrib>Hatano, Takashi</creatorcontrib><creatorcontrib>Takahashi, Hideaki</creatorcontrib><creatorcontrib>Nishimura, Goshi</creatorcontrib><creatorcontrib>Oridate, Nobuhiko</creatorcontrib><title>Effect of HER2‐targeted therapy on PDX and PDX‐derived organoids generated from HER2‐positive salivary duct carcinoma</title><title>Head &amp; neck</title><addtitle>Head Neck</addtitle><description>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. 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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. 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source Wiley-Blackwell Read & Publish Collection
subjects Apoptosis
Carcinoma
Cell proliferation
ErbB-2 protein
HER2
lapatinib
Oral cancer
Organoids
patient‐derived organoid
Phosphorylation
salivary duct carcinoma
salivary gland cancer
siRNA
title Effect of HER2‐targeted therapy on PDX and PDX‐derived organoids generated from HER2‐positive salivary duct carcinoma
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