Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

ABSTRACT: Original patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles. ICE-T refractory tumor are implanted and additional 6 arm treatment trial and control conducted based on genomic profiles of F2 generation mice to suggested therapies Original patient tumor expanded in F0 mouse generation to F1 generation for multiple arm therapy trial and then refractory tumors implanted for additional multiple arm therapy trial

ORGANISM(S): Homo sapiens

SUBMITTER: David Cherba

PROVIDER: E-GEOD-51130 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

Monsma David J DJ Cherba David M DM Richardson Patrick J PJ Vance Sean S Rangarajan Sanjeet S Dylewski Dawna D Eugster Emily E Scott Stephanie B SB Beuschel Nicole L NL Davidson Paula J PJ Axtell Richard R Mitchell Deanna D Lester Eric P EP Junewick Joseph J JJ Webb Craig P CP Monks Noel R NR

Pediatric blood & cancer 20140331 9

<h4>Background</h4>Precision (Personalized) medicine has the potential to revolutionize patient health care especially for many cancers where the fundamental disease etiology remains either elusive or has no available therapy. Here we outline a study in alveolar rhabdomyosarcoma, in which we use gene expression profiling and a series of drug prediction algorithms combined with a matched patient-derived xenograft (PDX) model to test bioinformatically predicted therapies.<h4>Procedure</h4>A PDX mo ...[more]

PMID: 24687871

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Project description:Head and neck squamous cell carcinoma (HNSCC) is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies for HNSCC and the understanding of its biology both depend upon clinically relevant animal models. An increasingly promising xenograft model, the patient derived xenograft (PDX), is developed by surgically implanting tumor tissue directly from a patient into an immunocompromised mouse. We transplanted 30 HNSCC primary tumors directly into mice. The histology and stromal components were analyzed using immunohistochemistry. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines. Five of 30 (17%) transplanted tumors could be serially passaged and used for therapeutic and mechanistic studies. One cell line has been established from a tongue primary. The tumors maintained the histologic appearance of the parent tumor although human stromal components were lost upon engraftment. One PDX model was derived from an HPV-positive tumor. From the >54,000 probes tested, there were widespread differences in gene expression between the tumors growing in mice vs. the corresponding human tumors from which they were derived. For genes differing between parent tumors and human cell lines in culture, the PDXs’ expression pattern was very similar to that of the parent tumors. There were also widespread expression differences between the human tumors that subsequently grew in mice vs. those that did not - suggesting that this model enriches for cancers with distinct biological features. Our results demonstrate the feasibility of a PDX model of HNSCC. Gene expression patterns suggest that the PDX more closely recapitulated the parental tumor than do cells in culture. The histology of the tumors in mice is similar to that of the same tumor in humans. Additionally, gene expression patterns and histology are stable over multiple generations. We transplanted HNSCC primary tumors directly into mice. Gene expression analysis with Affymetrix U133A-microarrays was conducted on patient tumors, including third generation and one tenth generation PDX; one PDX-derived cell line; and 2 established HNSCC cell lines.

Dataset Information

Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

Publications

Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

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