2016
DOI: 10.1007/s00280-016-3042-6
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Identifying novel therapeutic agents using xenograft models of pediatric cancer

Abstract: In the USA, the overall cure rate for all childhood cancers is seventy percent, and in many patients that ultimately fail curative therapy, initial responses to current multimodality treatments (surgery, radiation therapy and chemotherapy) is good, with overall 5-year event-free survival approaching 80 %. However, current approaches to curative therapy result in significant morbidity and long-term sequelae, including cardiac dysfunction and cognitive impairment. Furthermore, dose-intensive chemotherapy with co… Show more

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Cited by 13 publications
(8 citation statements)
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“…11,27 These models are predictive of clinical outcomes and therefore are an excellent platform for preclinical drug testing and as avatars for personalised medicine. 8,9,11 This study extends previous neuroblastoma PDX model establishment reports [19][20][21][22][23][24][25][26][27][28] by demonstrating that PDX models can also be developed from diagnostic cytogenetic culture without additional loss of fidelity, that more rapid engraftment can be achieved with orthoptic implantation and that additional sample processing can circumvent loss of models by xenogeneic GvHD.…”
Section: Discussionsupporting
confidence: 79%
See 1 more Smart Citation
“…11,27 These models are predictive of clinical outcomes and therefore are an excellent platform for preclinical drug testing and as avatars for personalised medicine. 8,9,11 This study extends previous neuroblastoma PDX model establishment reports [19][20][21][22][23][24][25][26][27][28] by demonstrating that PDX models can also be developed from diagnostic cytogenetic culture without additional loss of fidelity, that more rapid engraftment can be achieved with orthoptic implantation and that additional sample processing can circumvent loss of models by xenogeneic GvHD.…”
Section: Discussionsupporting
confidence: 79%
“…5,6 Realistic laboratory models that reflect the genetic diversity of high-risk neuroblastoma have an important role to play in preclinical assessment of new agents or combinations, in validating the relevance of mutations as actionable targets and in modelling the development of drug resistance. 7,8 For the individual patient, personalised or avatar models are playing an increasingly important role in personalised oncology. 9,10 Patient-derived xenograft (PDX) models are generated from the implantation of patient tumour sample directly into immunodeficient mice, and the subsequent passage of tumour material from animal to animal.…”
Section: Introductionmentioning
confidence: 99%
“…Patient‐derived xenografts (PDX) and all Ewing sarcoma cell lines were described . All EWS cell lines [ES1 (RRID: CVCL_1198), ES2 (RRID: CVCL_AX39), ES4 (RRID: CVCL_1200), ES6 (RRID: CVCL_1202), ES7 (RRID: CVCL_1203), ES8 (RRID: CVCL_1204), SKNEP1 (RRID: CVCL_0631), TC71 (RRID: CVCL_2213) and CHLA258 (RRID: CVCL_A058), and EW8 (RRID: CVCL_V618)] were maintained in RPMI supplemented with 10% FBS, 0.1 mM nonessential amino acids, sodium pyruvate, penicillin, streptomycin, l ‐glutamine (Thermo Fisher Scientific, Waltham, MA).…”
Section: Methodsmentioning
confidence: 99%
“…Patient-derived xenografts (PDX) and all Ewing sarcoma cell lines were described. 24 All EWS cell lines [ES1 (RRID: CVCL_1198), ES2 (RRID: CVCL_AX39), ES4 (RRID: CVCL_1200), ES6 (RRID: CVCL_1202), ES7 (RRID: CVCL_1203), ES8 (RRID: CVCL_1204), SKNEP1 (RRID: CVCL_0631), TC71 (RRID: CVCL_2213) and CHLA258 (RRID: CVCL_A058), and EW8 (RRID: CVCL_V618)] were maintained in RPMI supplemented with 10% FBS, 0.1 mM nonessential amino acids, sodium pyruvate, penicillin, streptomycin, L-glutamine (Thermo Fisher Scientific, Waltham, MA). GD2 negative A204 (RRID: CVCL_1058) rhabdomyosarcoma cells were purchased from ATCC (American Type Culture Collection, Manassas, VA) and were transduced with a gammaretroviral cassette coexpressing GD2 and GD3 synthases (Addgene, Plasmid #75013) to drive the biosynthesis of GD2 as described.…”
Section: Cell Lines and Mediamentioning
confidence: 99%
“…Promising results from these PDX models led to the National Cancer Institute-sponsored Pediatric Preclinical Testing Program (PPTP), which evaluated over 80 drugs or drug combinations in a range of pediatric cancer models (Houghton et al, 2007). Summary results from the PPTP were published recently (Geier et al, 2015;Jones et al, 2016;Kurmasheva and Houghton, 2016) and demonstrate some principles that may relate to how new agents are developed in pediatric cancer. The PDX models comprised kidney tumors (Wilms tumor and malignant rhabdoid tumors), sarcoma (Ewing, rhabdomyosarcoma, osteosarcoma), neuroblastoma, brain tumors (medulloblastoma, ependymoma, glioblastoma), and ALL, totaling about 50 models used for most of the drug testing.…”
Section: A Patient-derived Xenograftsmentioning
confidence: 99%