Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer.
Afatinib
/ administration & dosage
Aminopyridines
/ administration & dosage
Animals
Biopsy
Carcinoma, Squamous Cell
/ drug therapy
Gene Amplification
Gene Regulatory Networks
Genetic Variation
Head and Neck Neoplasms
/ drug therapy
High-Throughput Nucleotide Sequencing
Humans
Methotrexate
/ administration & dosage
Mice
Morpholines
/ administration & dosage
Papillomavirus Infections
/ drug therapy
Patient-Specific Modeling
Treatment Outcome
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Biomarker
Head and neck cancer
Patient-derived xenograft
Squamous cell cancer
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
15 Apr 2020
15 Apr 2020
Historique:
received:
17
12
2019
accepted:
25
03
2020
entrez:
16
4
2020
pubmed:
16
4
2020
medline:
19
12
2020
Statut:
epublish
Résumé
We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. 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. 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. Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
Sections du résumé
BACKGROUND
BACKGROUND
We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics.
METHODS
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
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
CONCLUSIONS
Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.
Identifiants
pubmed: 32293356
doi: 10.1186/s12885-020-06786-5
pii: 10.1186/s12885-020-06786-5
pmc: PMC7160896
doi:
Substances chimiques
Aminopyridines
0
Morpholines
0
NVP-BKM120
0
Afatinib
41UD74L59M
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
316Subventions
Organisme : Health Promotion Administration, Ministry of Health and Welfare (TW)
ID : HI15C1592
Organisme : Korea Carbon Capture and Sequestration R and D Center (KR)
ID : HI13C2162
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