Citation
All O-PDX models and associated data are available. While there is no obligation to collaborate when requesting these samples, we ask that you cite the following reference in publications resulting from use of CSTN resources:
Stewart, E,* Federico, S,* Chen, X,* et al, Orthotopic patient-derived xenografts of paediatric solid tumours. Nature. 2017 Sep 7;549(7670):96-100
Protocols
SOPs for processing and propagating O-PDX
ChIP Seq Protocols visualized in the epigenetic data browsers
PK Reports
Preclinical Pharmacokinetic (PK) data are available for a number of high-priority drugs being explored for activity against pediatric solid tumors. If interested in other drugs, please inquire using the Request form, and data will be provided if it’s available. Attached files and additional details may also be requested using the Request form.
Standard of Care regimens used in current preclinical trials are available in the Appendix. Data from completed preclinical Phase I (tolerability), Phase II (small pilot efficacy study) and Phase III (randomized, placebo-controlled) trials are available by request. For more details and descriptions of Phase I, II and III, please see Stewart et al, 2014 Cell Reports.
Publications
Patel AG, Chen X, Huang X, Clay MR, Komorova N, Krasin MJ, Pappo A, Tillman H, Orr BA, McEvoy J, Gordon B, Blankenship K, Reilly C, Zhou X, Norrie JL, Karlstrom A, Yu J, Wodarz D, Stewart E, Dyer MA. The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma. Dev Cell. 2022 May 23;57(10):1226-1240
Abstract | Full Text
Clay MR, Patel A, Tran Q, Hedges DJ, Chang TC, Stewart E, Charville G, Cline C, Dyer MA, Orr BA. Methylation profiling reveals novel molecular classes of rhabdomyosarcoma. Sci Rep. 2021 Nov 15;11(1):22213
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Norrie JL, Nityanandam A, Lai K, Chen X, Wilson M, Stewart E, Griffiths L, Jin H, Wu G, Orr B, Tran Q, Allen S, Reilly C, Zhou X, Zhang J, Newman K, Johnson D, Brennan R, Dyer MA. Retinoblastoma from human stem cell-derived retinal organoids. Nat Commun. 2021 Jul 27;12(1):4535
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Nguyen R, Patel AG, Griffiths LM, Dapper J, Stewart EA, Houston J, Johnson M, Akers WJ, Furman WL, Dyer MA. Next-generation humanized patient-derived xenograft mouse model for pre-clinical antibody studies in neuroblastoma. Cancer Immunol Immunother. 2021 Mar;70(3):721-732
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Slyper* M, Porter* CBM, Ashenberg*O, Waldman J, Drokhlyansky E, Wakiro I, Smillie C, Smith-Rosario G, Wu J, Dionne D, Vigneau S, Jané-Valbuena J, Tickle TL, Napolitano S, Su MJ, Patel AG, Karlstrom A, Gritsch S, Nomura M, Waghray A, Gohil SH, Tsankov AM, Jerby-Arnon L, Cohen O, Klughammer J, Rosen Y, Gould J, Nguyen L, Hofree M, Tramontozzi PJ, Li B, Wu CJ, Izar B, Haq R, Hodi FS, Yoon CH, Hata AN, Baker SJ, Suvà ML, Bueno R, Stover EH, Clay MR, Dyer MA, Collins NB, Matulonis UA, Wagle N, Johnson BE, Rotem A, Rozenblatt-Rosen O, Regev A. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors. Nat Med. 2020 May;26(5):792-802
Abstract | Full Text
Zeineldin M, Federico S, Chen X, Fan Y, Xu B, Stewart E, Zhou X, Jeon J, Griffiths L, Nguyen R, Norrie J, Easton J, Mulder H, Yergeau D, Liu Y, Wu J, Van Ryn C, Naranjo A, Hogarty MD, Kamiński MM, Valentine M, Pruett-Miller SM, Pappo A, Zhang J, Clay MR, Bahrami A, Vogel P, Lee S, Shelat A, Sarthy JF, Meers MP, George RE, Mardis ER, Wilson RK, Henikoff S, Downing JR, Dyer MA. MYCN amplification and ATRX mutations are incompatible in neuroblastoma. Nat Commun. 2020 Feb 14;11(1):913
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Qadeer ZA, Valle-Garcia D, Hasson D, Sun Z, Cook A, Nguyen C, Soriano A, Ma A, Griffiths LM, Zeineldin M, Filipescu D, Jubierre L, Chowdhury A, Deevy O, Chen X, Finkelstein DB, Bahrami A, Stewart E, Federico S, Gallego S, Dekio F, Fowkes M, Meni D, Maris JM, Weiss WA, Roberts SS, Cheung NV, Jin J, Segura MF, Dyer MA, Bernstein E. ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures. Cancer Cell. 2019 Nov 11;36(5):512-527
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Brady SW, Ma X, Bahrami A, Satas G, Wu G, Newman S, Rusch M, Putnam DK, Mulder HL, Yergeau DA, Edmonson MN, Easton J, Alexandrov LB, Chen X, Mardis ER, Wilson RK, Downing JR, Pappo AS, Raphael BJ, Dyer MA, Zhang J. The Clonal Evolution of Metastatic Osteosarcoma as Shaped by Cisplatin Treatment. Mol Cancer Res. 2019 Apr;17(4):895-906
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Nguyen R, Moustaki A, Norrie JL, Brown S, Akers WJ, Shirinifard A, Dyer MA. Interleukin-15 Enhances Anti-GD2 Antibody-Mediated Cytotoxicity in an Orthotopic PDX Model of Neuroblastoma. Clin Cancer Res. 2019 Dec 15;25(24):7554-7564
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Loh AHP, Stewart E, Bradley CL, Chen X, Daryani V, Stewart CF, Calabrese C, Funk A, Miller G, Karlstrom A, Krafcik F, Goshorn DR, Vogel P, Bahrami A, Shelat A, Dyer MA. Combinatorial screening using orthotopic patient derived xenograft-expanded early phase cultures of osteosarcoma identify novel therapeutic drug combinations. Cancer Lett 2019.
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Stewart*, McEvoy*, Wang*, Chen*, et al, Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses Cancer Cell 2018.
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Stewart E, et al, The Childhood Solid Tumor Network: A new resource for the developmental biology and oncology research communities. Dev. Biol 2016.
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Stewart E, et al, Development and characterization of a human orthotopic neuroblastoma xenograft. Developmental Biology 2016.
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Pinto EM, et al, Genomic landscape of paediatric adrenocortical tumours. Nat Commun 2015.
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Lu C, et al, The genomic landscape of childhood and adolescent melanoma. J Invest Dermatol 2015.
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Stewart E, et al, Targeting the DNA Repair Pathway in Ewing Sarcoma. Cell Reports 2014.
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Tirode F, et al, Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 2014.
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Chen X, et al, Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep 2014.
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Chen X, et al, Targeting oxidative stress in embryonal rhabdomyosarcoma. Cancer Cell 2013.
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Cheung NK, et al, Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 2012.
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Zhang J, et al, A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature 2012.
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