{"doi":"10.1101/2022.04.29.490078","title":"<i>Ex vivo</i> to <i>in vivo</i> model of malignant peripheral nerve sheath tumors for precision oncology","abstract":"Abstract Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1-MPNST), but can occur sporadically. Through a multi-institution collaboration, we have developed 13 NF1-associated MPNST patient-derived xenografts (PDX). Genomic analysis of the PDX-tumor pairs identified somatic mutations in NF1 (61%), SUZ12 (61%), EED (15%), and TP53 (15%), and chromosome 8 (Chr8) gain (77%), consistent with published data. Pre-clinical models that capture this molecular heterogeneity are needed to identify and prioritize effective drug candidates for clinical translation. Here, we describe the successful development of a medium-throughput ex vivo 3D microtissue model with several advantages over 2D cell line growth, which can be utilized to predict drug response in vivo . Herein, we present proof-of-principle of this PDX-to-microtissue system, using four genomically representative MPNST and three drugs. This work highlights the development of a novel ex vivo to in vivo preclinical platform in MPNST that successfully captures the genomic diversity observed in patients and represents a resource to identify future therapeutic strategies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303232,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9148,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":417673,"name":"Alex T. Larsson","orcid":"0000-0002-1350-8271","position":1,"is_corresponding":false},{"id":357086,"name":"Ana Calizo","orcid":"0000-0002-2581-6378","position":2,"is_corresponding":false},{"id":315352,"name":"Kai Pollard","orcid":"0000-0002-2778-8884","position":3,"is_corresponding":false},{"id":80022,"name":"Xiaochun Zhang","orcid":"0000-0002-9816-1034","position":4,"is_corresponding":false},{"id":995846,"name":"Eric Conniff","orcid":null,"position":5,"is_corresponding":false},{"id":995847,"name":"Justin Tibbitts","orcid":null,"position":6,"is_corresponding":false},{"id":475468,"name":"Sara H. Osum","orcid":"0000-0002-4548-5422","position":7,"is_corresponding":false},{"id":417678,"name":"Kyle Williams","orcid":"0000-0003-4333-9111","position":8,"is_corresponding":false},{"id":995848,"name":"Ali L. Crampton","orcid":null,"position":9,"is_corresponding":false},{"id":995476,"name":"Tyler Jubenville","orcid":"0009-0003-9578-4847","position":10,"is_corresponding":false},{"id":995477,"name":"Daniel Schefer","orcid":"0000-0003-2447-0157","position":11,"is_corresponding":false},{"id":678140,"name":"Kuangying Yang","orcid":"0000-0002-6992-9585","position":12,"is_corresponding":false},{"id":625872,"name":"Yang Lyu","orcid":"0000-0002-4353-0082","position":13,"is_corresponding":false},{"id":995478,"name":"Jessica Bade","orcid":"0000-0001-7595-0017","position":14,"is_corresponding":false},{"id":787866,"name":"James C. Pino","orcid":"0000-0001-9882-6748","position":15,"is_corresponding":false},{"id":11491,"name":"Sara J. C. Gosline","orcid":"0000-0002-6534-4774","position":16,"is_corresponding":false},{"id":80024,"name":"Christine A. Pratilas","orcid":"0000-0002-7116-0605","position":17,"is_corresponding":false},{"id":257760,"name":"David A. Largaespada","orcid":"0000-0002-3183-0491","position":18,"is_corresponding":false},{"id":469592,"name":"David K. Wood","orcid":"0000-0001-5225-2144","position":19,"is_corresponding":false},{"id":80026,"name":"Angela C. Hirbe","orcid":"0000-0003-1719-0771","position":20,"is_corresponding":false},{"id":995475,"name":"Himanshi Bhatia","orcid":"0000-0001-9949-3412","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T00:32:24.307938Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}