Evidence map›Paper›PMID 33510214›Full record

ArticleScientific reports2021

Development and characterization of patient-derived xenografts from non-small cell lung cancer brain metastases.

Andrew M Baschnagel, Saakshi Kaushik, Arda Durmaz, Steve Goldstein, Irene M Ong, Lindsey Abel, Paul A Clark, Zafer Gurel, Ticiana Leal, Darya Buehler and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 36 citations in OpenAlex.

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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

13 authors at 3 institutions in 1 country.

Andrew M BaschnagelDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA. baschnagel@humonc.wisc.edu.
Saakshi KaushikDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA.
Arda DurmazCase Western Reserve University, Cleveland, OH, 44195, USA.
Steve GoldsteinUniversity of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Irene M OngUniversity of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Lindsey AbelDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA.
Paul A ClarkDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA.
Zafer GurelDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA.
Ticiana LealUniversity of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Darya BuehlerUniversity of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
Gopal IyerDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA.
Jacob G ScottDepartment of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, 10201 Carnegie Ave, Cleveland, OH, 44195, USA.
Randall J KimpleDepartment of Human Oncology, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, K4/B100-0600, Madison, WI, 53792, USA. rkimple@humonc.wisc.edu.
University of Wisconsin–Madison · USCase Western Reserve University · USCleveland Clinic · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
NCI NIH HHS P30 CA014520
6 · The paper itself

Abstract

Non-small cell lung cancer (NSCLC) brain metastasis cell lines and in vivo models are not widely accessible. Herein we report on a direct-from patient-derived xenograft (PDX) model system of NSCLC brain metastases with genomic annotation useful for translational and mechanistic studies. Both heterotopic and orthotopic intracranial xenografts were established and RNA and DNA sequencing was performed on patient and matching tumors. Morphologically, strong retention of cytoarchitectural features was observed between original patient tumors and PDXs. Transcriptome and mutation analysis revealed high correlation between matched patient and PDX samples with more than more than 95% of variants detected being retained in the matched PDXs. PDXs demonstrated response to radiation, response to selumetinib in tumors harboring KRAS G12C mutations and response to savolitinib in a tumor with MET exon 14 skipping mutation. Savolitinib also demonstrated in vivo radiation enhancement in our MET exon 14 mutated PDX. Early passage cell strains showed high consistency between patient and PDX tumors. Together, these data describe a robust human xenograft model system for investigating NSCLC brain metastases. These PDXs and cell lines show strong phenotypic and molecular correlation with the original patient tumors and provide a valuable resource for testing preclinical therapeutics.

Indexed as

Disease Models, AnimalHeterograftsAllelesAnimalsAntineoplastic AgentsBiopsyBrain NeoplasmsCarcinoma, Non-Small-Cell LungCell Line, TumorGene Expression ProfilingGenes, ReporterHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryLung NeoplasmsProtein Kinase InhibitorsAntineoplastic AgentsProtein Kinase Inhibitors

Identifiers

PMID33510214
PMCPMC7843608
OpenAlexW3125834563

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.