Evidence map›Paper›PMID 37246765›Full record

ArticleNeuro-oncology2023

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology.

Alex T Larsson, Himanshi Bhatia, Ana Calizo, Kai Pollard, Xiaochun Zhang, Eric Conniff, Justin F Tibbitts, Elizabeth Rono, Katherine Cummins, Sara H Osum and 18 more

Open access · hybridAbstract read
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 14 citations in OpenAlex.

  1. Drug sensitivity testing of patient-derived bone sarcomas identifies selective kinase inhibitors for patients with refractory disease.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  2. Article
  3. Article
  4. Review
  5. MTA-Cooperative PRMT5 Inhibitors Are Efficacious in MTAP-Deleted Malignant Peripheral Nerve Sheath Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  6. Article
  7. Article
  8. DLK1 Distinguishes Subsets of NF1-Associated Malignant Peripheral Nerve Sheath Tumors with Divergent Molecular Signatures.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
  9. Review
  10. Review
  11. Contemporary Approach to Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 1 country.

Alex T LarssonDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-1350-8271
Himanshi BhatiaDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
Ana CalizoDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kai PollardDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xiaochun ZhangDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
Eric ConniffDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Justin F TibbittsDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Elizabeth RonoDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Katherine CumminsDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Sara H OsumDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Kyle B WilliamsDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Alexandra L CramptonDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Tyler JubenvilleDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Daniel ScheferDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
Kuangying YangDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
Yang LyuDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
James C PinoPacific Northwest National Laboratory, Seattle, Washington, USA.
Jessica BadePacific Northwest National Laboratory, Seattle, Washington, USA.
John M GrossDepartment of Pathology, Division of Surgical Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Alla LisokDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Carina A DehnerDepartment of Pathology and Immunology, Washington University in St. Louis, Missouri, USA.
John S A ChrisingerDepartment of Pathology and Immunology, Washington University in St. Louis, Missouri, USA.
Kevin HeDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
Sara J C GoslinePacific Northwest National Laboratory, Seattle, Washington, USA.
Christine A PratilasDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
David A LargaespadaDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
David K WoodDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Angela C HirbeDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.ORCID 0000-0003-1719-0771
Washington University in St. Louis · USUniversity of Minnesota Medical Center · USUniversity of Minnesota · USJohns Hopkins University · USPacific Northwest National Laboratory · USJohns Hopkins Hospital · US

Funding

Uncovering treatment targets for peripheral nerve sheath tumor progression in NF1R01NS115438 · NINDS · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, RATNER, NANCY · 2020 to 2024
$2.9M
Recurrent Tumor-Specific Alternately Processed Transcripts as a Source of Neoantigens for NF1-associated Malignant Peripheral Nerve Sheath Tumor ImmunopreventionUH3CA244687 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW · 2021 to 2023
$2.1M
NCI NIH HHS UH3 CA244687NINDS NIH HHS R01 NS115438
6 · The paper itself

Abstract

backgroundMalignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).

methodsGenomic analysis was performed on all PDX-tumor pairs. Selected PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, and mirdametinib) ex vivo and in vivo. For 3D microtissue studies, cell viability was the endpoint as assessed by Zeiss Axio Observer. For PDX drug studies, tumor volume was measured twice weekly. Bulk RNA sequencing was performed to identify pathways enriched in cells.

resultsWe developed 13 NF1-associated MPNST-PDX and identified mutations or structural abnormalities in NF1 (100%), SUZ12 (85%), EED (15%), TP53 (15%), CDKN2A (85%), and chromosome 8 gain (77%). We successfully assembled PDX into 3D microtissues, categorized as robust (>90% viability at 48 h), good (>50%), or unusable (<50%). We evaluated drug response to "robust" or "good" microtissues, namely MN-2, JH-2-002, JH-2-079-c, and WU-225. Drug response ex vivo predicted drug response in vivo, and enhanced drug effects were observed in select models.

conclusionsThese data support the successful establishment of a novel 3D platform for drug discovery and MPNST biology exploration in a system representative of the human condition.

Indexed as

Nerve Sheath NeoplasmsNeurofibromatosis 1NeurofibrosarcomaHumansMutationPrecision Medicine3D microtissuesdrug screeninggenomic variantsMPNSTNF1PDX

Identifiers

PMID37246765
PMCPMC10628938
OpenAlexW4378640489

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.