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Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Sun, H; Cao, S; Mashl, RJ; Mo, C-K; Zaccaria, S; Wendl, MC; Davies, SR; ... Ding, L; + view all (2021) Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment. Nature Communications , 12 , Article 5086. 10.1038/s41467-021-25177-3. Green open access

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Abstract

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.

Type: Article
Title: Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-021-25177-3
Publisher version: https://doi.org/10.1038/s41467-021-25177-3
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Animals, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Genome, Genomics, Heterografts, Humans, Male, Mice, Models, Biological, Mutation, Neoplasms, Transcriptome, Xenograft Model Antitumor Assays
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10135516
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