Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer
Abstract 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 implantatio...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-06786-5 |
| _version_ | 1818639883639455744 |
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| author | Han Na Kang Jae-Hwan Kim A-Young Park Jae Woo Choi Sun Min Lim Jinna Kim Eun Joo Shin Min Hee Hong Kyoung-Ho Pyo Mi Ran Yun Dong Hwi Kim Hanna Lee Sun Och Yoon Da Hee Kim Young Min Park Hyung Kwon Byeon Inkyung Jung Soonmyung Paik Yoon Woo Koh Byoung Chul Cho Hye Ryun Kim |
| author_facet | Han Na Kang Jae-Hwan Kim A-Young Park Jae Woo Choi Sun Min Lim Jinna Kim Eun Joo Shin Min Hee Hong Kyoung-Ho Pyo Mi Ran Yun Dong Hwi Kim Hanna Lee Sun Och Yoon Da Hee Kim Young Min Park Hyung Kwon Byeon Inkyung Jung Soonmyung Paik Yoon Woo Koh Byoung Chul Cho Hye Ryun Kim |
| author_sort | Han Na Kang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-16T23:02:27Z |
| format | Article |
| id | doaj.art-d789d28930c4424bb99a3602f9eb9a8f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-16T23:02:27Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d789d28930c4424bb99a3602f9eb9a8f2022-12-21T22:12:42ZengBMCBMC Cancer1471-24072020-04-0120111210.1186/s12885-020-06786-5Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancerHan Na Kang0Jae-Hwan Kim1A-Young Park2Jae Woo Choi3Sun Min Lim4Jinna Kim5Eun Joo Shin6Min Hee Hong7Kyoung-Ho Pyo8Mi Ran Yun9Dong Hwi Kim10Hanna Lee11Sun Och Yoon12Da Hee Kim13Young Min Park14Hyung Kwon Byeon15Inkyung Jung16Soonmyung Paik17Yoon Woo Koh18Byoung Chul Cho19Hye Ryun Kim20JE-UK Institute for Cancer Research, JEUK Co. Ltd.JE-UK Institute for Cancer Research, JEUK Co. Ltd.JE-UK Institute for Cancer Research, JEUK Co. Ltd.JE-UK Institute for Cancer Research, JEUK Co. Ltd.Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical CenterDepartment of Pathology, Yonsei University College of MedicineJE-UK Institute for Cancer Research, JEUK Co. Ltd.Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of MedicineJE-UK Institute for Cancer Research, JEUK Co. Ltd.JE-UK Institute for Cancer Research, JEUK Co. Ltd.JE-UK Institute for Cancer Research, JEUK Co. Ltd.Severance Biomedical Science Institute, Yonsei University College of MedicineDepartment of Radiology, Severance Hospital, Yonsei University College of MedicineDepartment of Otorhinolaryngology, Yonsei University College of MedicineDepartment of Otorhinolaryngology, Yonsei University College of MedicineDepartment of Otolaryngology-Head and Neck Surgery Korea, University College of MedicineDepartment of Biostatistics and Medical Informatics, Yonsei University College of MedicineSeverance Biomedical Science Institute, Yonsei University College of MedicineDepartment of Otorhinolaryngology, Yonsei University College of MedicineJE-UK Institute for Cancer Research, JEUK Co. Ltd.Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12885-020-06786-5Patient-derived xenograftBiomarkerHead and neck cancerSquamous cell cancer |
| spellingShingle | Han Na Kang Jae-Hwan Kim A-Young Park Jae Woo Choi Sun Min Lim Jinna Kim Eun Joo Shin Min Hee Hong Kyoung-Ho Pyo Mi Ran Yun Dong Hwi Kim Hanna Lee Sun Och Yoon Da Hee Kim Young Min Park Hyung Kwon Byeon Inkyung Jung Soonmyung Paik Yoon Woo Koh Byoung Chul Cho Hye Ryun Kim Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer BMC Cancer Patient-derived xenograft Biomarker Head and neck cancer Squamous cell 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 | Patient-derived xenograft Biomarker Head and neck cancer Squamous cell cancer |
| url | http://link.springer.com/article/10.1186/s12885-020-06786-5 |
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