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Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We e...

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Autores principales: Kang, Han Na, Kim, Jae-Hwan, Park, A-Young, Choi, Jae Woo, Lim, Sun Min, Kim, Jinna, Shin, Eun Joo, Hong, Min Hee, Pyo, Kyoung-Ho, Yun, Mi Ran, Kim, Dong Hwi, Lee, Hanna, Yoon, Sun Och, Kim, Da Hee, Park, Young Min, Byeon, Hyung Kwon, Jung, Inkyung, Paik, Soonmyung, Koh, Yoon Woo, Cho, Byoung Chul, Kim, Hye Ryun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160896/
https://www.ncbi.nlm.nih.gov/pubmed/32293356
http://dx.doi.org/10.1186/s12885-020-06786-5
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author Kang, Han Na
Kim, Jae-Hwan
Park, A-Young
Choi, Jae Woo
Lim, Sun Min
Kim, Jinna
Shin, Eun Joo
Hong, Min Hee
Pyo, Kyoung-Ho
Yun, Mi Ran
Kim, Dong Hwi
Lee, Hanna
Yoon, Sun Och
Kim, Da Hee
Park, Young Min
Byeon, Hyung Kwon
Jung, Inkyung
Paik, Soonmyung
Koh, Yoon Woo
Cho, Byoung Chul
Kim, Hye Ryun
author_facet Kang, Han Na
Kim, Jae-Hwan
Park, A-Young
Choi, Jae Woo
Lim, Sun Min
Kim, Jinna
Shin, Eun Joo
Hong, Min Hee
Pyo, Kyoung-Ho
Yun, Mi Ran
Kim, Dong Hwi
Lee, Hanna
Yoon, Sun Och
Kim, Da Hee
Park, Young Min
Byeon, Hyung Kwon
Jung, Inkyung
Paik, Soonmyung
Koh, Yoon Woo
Cho, Byoung Chul
Kim, Hye Ryun
author_sort Kang, Han Na
collection PubMed
description BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
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spelling pubmed-71608962020-04-21 Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer Kang, Han Na Kim, Jae-Hwan Park, A-Young Choi, Jae Woo Lim, Sun Min Kim, Jinna Shin, Eun Joo Hong, Min Hee Pyo, Kyoung-Ho Yun, Mi Ran Kim, Dong Hwi Lee, Hanna Yoon, Sun Och Kim, Da Hee Park, Young Min Byeon, Hyung Kwon Jung, Inkyung Paik, Soonmyung Koh, Yoon Woo Cho, Byoung Chul Kim, Hye Ryun BMC Cancer Research Article BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery. BioMed Central 2020-04-15 /pmc/articles/PMC7160896/ /pubmed/32293356 http://dx.doi.org/10.1186/s12885-020-06786-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Kang, Han Na
Kim, Jae-Hwan
Park, A-Young
Choi, Jae Woo
Lim, Sun Min
Kim, Jinna
Shin, Eun Joo
Hong, Min Hee
Pyo, Kyoung-Ho
Yun, Mi Ran
Kim, Dong Hwi
Lee, Hanna
Yoon, Sun Och
Kim, Da Hee
Park, Young Min
Byeon, Hyung Kwon
Jung, Inkyung
Paik, Soonmyung
Koh, Yoon Woo
Cho, Byoung Chul
Kim, Hye Ryun
Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title_full Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title_fullStr Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title_full_unstemmed Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title_short Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
title_sort establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160896/
https://www.ncbi.nlm.nih.gov/pubmed/32293356
http://dx.doi.org/10.1186/s12885-020-06786-5
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