Back to Search
Start Over
Orthotopic Patient-Derived Xenografts of Pediatric Solid Tumors
- Source :
- Nature
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 14764687 and 00280836
- Volume :
- 549
- Issue :
- 7670
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....2082ebbf9f6392081c9eedc9807c936f