Orthotopic Patient-Derived Xenografts of Pediatric Solid Tumors
Autor: | Cori Bradley, Jason Dapper, Xin Zhou, Jianrong Wu, Armita Bahrami, James R. Downing, Sara M. Federico, Elizabeth Stewart, Asa Karlstrom, Alberto S. Pappo, Nathaniel R. Twarog, Kaley Blankenship, Anang A. Shelat, Jinghui Zhang, Burgess B. Freeman, Victoria Honnell, Richard K. Wilson, Monica Ocarz, John Easton, Beisi Xu, Brittney Gordon, Michael A. Dyer, Xiang Chen, Elaine R. Mardis, Michael R. Clay |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Vincristine Indoles Autopsy Cell Cycle Proteins Pyrimidinones Hydroxamic Acids Irinotecan Article Epigenesis Genetic Bortezomib 03 medical and health sciences chemistry.chemical_compound Mice In vivo Panobinostat Neoplasms Rhabdomyosarcoma medicine Animals Humans Cancer epigenetics Child Multidisciplinary business.industry Cancer Nuclear Proteins Protein-Tyrosine Kinases medicine.disease Xenograft Model Antitumor Assays 3. Good health Clone Cells High-Throughput Screening Assays 030104 developmental biology Pyrimidines chemistry Immunology Cancer research Heterografts Pyrazoles Camptothecin Drug Therapy Combination Female business medicine.drug |
Zdroj: | Nature |
ISSN: | 1476-4687 0028-0836 |
Popis: | Paediatric solid tumours arise from endodermal, ectodermal, or mesodermal lineages. Although the overall survival of children with solid tumours is 75%, that of children with recurrent disease is below 30%. To capture the complexity and diversity of paediatric solid tumours and establish new models of recurrent disease, here we develop a protocol to produce orthotopic patient-derived xenografts at diagnosis, recurrence, and autopsy. Tumour specimens were received from 168 patients, and 67 orthotopic patient-derived xenografts were established for 12 types of cancer. The origins of the patient-derived xenograft tumours were reflected in their gene-expression profiles and epigenomes. Genomic profiling of the tumours, including detailed clonal analysis, was performed to determine whether the clonal population in the xenograft recapitulated the patient's tumour. We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo. |
Databáze: | OpenAIRE |
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