Characterization and radiosensitivity of HPV-related oropharyngeal squamous cell carcinoma patient-derived xenografts
| Autor: | Benedicte Parm Ulhøi, Morten Busk, Magnus Stougaard, Pernille Lassen, Viveque Egsgaard Nielsen, M.S. Thomsen, Jens Overgaard, Jan Alsner, Torben Steiniche, J. Lilja-Fischer |
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| Rok vydání: | 2019 |
| Předmět: |
Male
EXPRESSION IMPACT medicine.medical_treatment Oropharynx Gene mutation Radiation Tolerance 030218 nuclear medicine & medical imaging Mice 03 medical and health sciences 0302 clinical medicine NECK-CANCER Cancer stem cell Biomarkers Tumor Animals Humans Medicine Radiology Nuclear Medicine and imaging Radiosensitivity HEAD Papillomaviridae Aged Squamous Cell Carcinoma of Head and Neck business.industry TUMOR XENOGRAFTS Papillomavirus Infections Head and neck cancer HUMAN-PAPILLOMAVIRUS Cancer Hematology General Medicine Middle Aged medicine.disease Xenograft Model Antitumor Assays Primary tumor Radiation therapy MODEL Oropharyngeal Neoplasms Oncology CLASSIFIER 030220 oncology & carcinogenesis Cancer research SURVIVAL Biomarker (medicine) Female business RADIOTHERAPY |
| Zdroj: | Lilja-Fischer, J K, Ulhøi, B P, Alsner, J, Stougaard, M, Thomsen, M S, Busk, M, Lassen, P, Steiniche, T, Nielsen, V E & Overgaard, J 2019, ' Characterization and radiosensitivity of HPV-related oropharyngeal squamous cell carcinoma patient-derived xenografts ', Acta Oncologica, vol. 58, no. 10, pp. 1489-1494 . https://doi.org/10.1080/0284186X.2019.1660802 Lilja-Fischer, J K, Ulhøi, B P, Alsner, J, Stougaard, M, Thomsen, M S, Busk, M, Lassen, P, Steiniche, T, Nielsen, V E & Overgaard, J 2019, ' Characterization and radiosensitivity of HPV-related oropharyngeal squamous cell carcinoma patient-derived xenografts ', Acta oncologica (Stockholm, Sweden), vol. 58, no. 10, pp. 1489-1494 . https://doi.org/10.1080/0284186X.2019.1660802 |
| DOI: | 10.6084/m9.figshare.9810320.v1 |
| Popis: | Background: Oropharyngeal squamous cell carcinomas (OPSCC) are rising rapidly in incidence due to Human Papillomavirus (HPV) and/or tobacco smoking. Prognosis is better for patients with HPV-positive disease, but may also be influenced by tobacco smoking and other factors. There is a need to individualize treatment to minimize morbidity and improve prognosis. Patient-derived xenografts (PDX) is an emerging pre-clinical research model that may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of PDX models, compare PDX tumors to the human original, and assess the suitability of this model for radiotherapy research and biomarker development. Material and methods: Tumor biopsies from 34 patients with previously untreated OPSCC were implanted in immunodeficient mice, giving rise to 12 squamous cell carcinoma PDX models (7 HPV+, 5 HPV-). Primary and PDX tumors were characterized extensively, examining histology, immunohistochemistry, cancer gene sequencing and gene expression analysis. Radiosensitivity was assessed in vivo in a growth delay assay. Results: Established PDX models maintained histological and immunohistochemical characteristics as well as HPV-status of the primary tumor. Important cancer driver gene mutations, e.g., in TP53, PIK3CA and others, were preserved. Gene expression related to cancer stem cell markers and gene expression subtype were preserved, while gene expression related to hypoxia and immune response differed. Radiosensitivity studies showed high concordance with clinical observations. Conclusion: PDX from OPSCC preserves important molecular characteristics of the human primary tumor. Radiosensitivity were in accordance with clinically observed treatment response. The PDX model is a clinically relevant surrogate model of head and neck cancer. Perspectives include increased understanding of disease biology, which could lead to development of novel treatments and biomarkers. |
| Databáze: | OpenAIRE |
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