Evidence map›Paper›PMID 38652658›Full record

ArticleCell reports2024

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.

Yim Ling Cheng, Matei A Banu, Wenting Zhao, Steven S Rosenfeld, Peter Canoll, Peter A Sims

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Kinesin Spindle Protein (KIF11) in Mitosis and Cancer.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Yim Ling ChengDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Matei A BanuDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Wenting ZhaoDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Steven S RosenfeldDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.
Peter CanollDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter A SimsDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: pas2182@columbia.edu.
Columbia University Irving Medical Center · USMayo Clinic in Florida · US

Funding

Systems Biology of Tumor Progression and Drug ResistanceU01CA168426 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2016
$6.5M
Elucidating and Targeting tumor dependencies and drug resistance determinants at the single cell levelU01CA272610 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2022 to 2026
$4.8M
Single Cell Analysis of the Infiltrative Margins of Glioblastoma and Post Treatment RecurrenceR01NS103473 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JEFFREY N BRUCE, Peter Canoll · 2017 to 2026
$4.3M
Targeting Go and Grow in GlioblastomaR01NS118513 · NINDS · MAYO CLINIC JACKSONVILLE · PI CANOLL, PETER, KENCHAPPA, RAJAPPA · 2020 to 2024
$2.8M
High Performance Computing Cluster for Biomedical ResearchS10OD032433 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2023 to 2023
$2.0M
NCI NIH HHS U01 CA168426NCI NIH HHS U01 CA272610NIH HHS S10 OD032433NINDS NIH HHS R01 NS103473NINDS NIH HHS R01 NS118513
6 · The paper itself

Abstract

Glioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target with roles in proliferation and invasion. Resistance to KIF11 inhibitors, which has mainly been studied in animal models, presents significant challenges. We use lineage-tracing barcodes and single-cell RNA sequencing to analyze resistance in patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor. Similar to GBM progression in patients, untreated cells lose their neural lineage identity and become mesenchymal, which is associated with poor prognosis. Conversely, cells subjected to long-term ispinesib treatment exhibit a proneural phenotype. We generate patient-derived xenografts and show that ispinesib-resistant cells form less aggressive tumors in vivo, even in the absence of drug. Moreover, treatment of human ex vivo GBM slices with ispinesib demonstrates phenotypic alignment with in vitro responses, underscoring the clinical relevance of our findings. Finally, using retrospective lineage tracing, we identify drugs that are synergistic with ispinesib.

Indexed as

Cell LineageDrug Resistance, NeoplasmGlioblastomaKinesinsSingle-Cell AnalysisAnimalsBrain NeoplasmsCell Line, TumorHumansMiceMitosisKIF11 protein, humanKinesinsCP: CancerCP: Cell biologydrug resistanceglioblastomamitotic kinesinsmultiplexed lineage tracingsingle-cell genomics

Identifiers

PMID38652658
PMCPMC11199018
OpenAlexW4394986431

What OpenQuestion holds

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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.