Evidence map›Paper›PMID 39095594›Full record

ArticleNature medicine2024

Targeting axonal guidance dependencies in glioblastoma with ROBO1 CAR T cells.

Chirayu R Chokshi, Muhammad Vaseem Shaikh, Benjamin Brakel, Martin A Rossotti, David Tieu, William Maich, Alisha Anand, Shawn C Chafe, Kui Zhai, Yujin Suk and 33 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. CD47 stabilizes ROBO2 to regulate glioblastoma progression by preventing ITCH-mediated ubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
  8. Humanized mouse models ofOncoimmunology · 2025
    Article
  9. Review
  10. Review
  11. From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Brain Tumor Stem Cells: New Perspectives.Methods in molecular biology (Clifton, N.J.) · 2025
    Review
  19. Review
  20. Immunotherapy in Glioblastoma: An Overview of Current Status.Clinical pharmacology : advances and applications · 2025
    Review
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

43 authors.

Chirayu R ChokshiDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.ORCID http://orcid.org/0000-0003-0831-0217
Muhammad Vaseem Shaikh *Centre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Benjamin Brakel *Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Martin A RossottiHuman Health Therapeutics Research Centre, Life Sciences Division, National Research Council Canada, Ottawa, ON, Canada.
David TieuDonnelly Centre, University of Toronto, Toronto, ON, Canada.
William MaichDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Alisha AnandDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Shawn C ChafeCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Kui ZhaiCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Yujin SukDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Agata M KieliszekDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Petar MileticCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Nicholas MikolajewiczProgram for Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-7525-0384
David ChenProgram for Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON, Canada.
Jamie D McNicolMcMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
Katherine ChanProgram for Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON, Canada.ORCID http://orcid.org/0009-0000-7513-5880
Amy H Y TongDonnelly Centre, University of Toronto, Toronto, ON, Canada.
Laura KuhlmannPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Lina LiuDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Zahra AlizadaCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Daniel MobilioDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Nazanin TatariDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Neil SavageDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Nikoo AghaeiDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Shan GrewalDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Anish PuriDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Minomi SubapandithaDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Dillon McKennaCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Vladimir IgnatchenkoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Joseph M SalamounDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Jacek M KwiecienDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Peter WipfDepartment of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7693-5863
Elizabeth R SharlowDepartment of Pharmacology, Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, VA, USA.
John P ProviasDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Jian-Qiang LuDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.ORCID http://orcid.org/0000-0003-1945-5569
John S LazoDepartment of Pharmacology, Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-0645-4025
Thomas KislingerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-3525-5540
Yu LuCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Kevin R BrownProgram for Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON, Canada.
Chitra VenugopalCentre for Discovery in Cancer Research (CDCR), McMaster University, Hamilton, ON, Canada.
Kevin A HenryHuman Health Therapeutics Research Centre, Life Sciences Division, National Research Council Canada, Ottawa, ON, Canada.
Jason MoffatDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada. jason.moffat@sickkids.ca.ORCID http://orcid.org/0000-0002-5663-8586
Sheila K SinghDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada. ssingh@mcmaster.ca.ORCID http://orcid.org/0000-0003-1272-5300

Funding

Developing small molecule PTP4A3 inhibitors for ovarian cancerR43CA228774 · NCI · KEVIRX INC. · PI LAZO, JOHN S. · 2019 to 2019
$289k
Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) PJT-438323Mitacs IT11823Mitacs IT15477NCI NIH HHS R43 CA228774Terry Fox Research Institute (Institut de Recherche Terry Fox) 1065
6 · The paper itself

Abstract

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2 (protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood-brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50-100% of mice. Our study identifies a promising multi-targetable PTP4A-ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors.

Indexed as

Brain NeoplasmsGlioblastomaReceptors, ImmunologicRoundabout ProteinsAnimalsCell Line, TumorFemaleHumansImmunotherapy, AdoptiveMiceNeoplasm Recurrence, LocalNerve Tissue ProteinsProtein Tyrosine PhosphatasesReceptors, Chimeric AntigenSignal TransductionT-LymphocytesNerve Tissue ProteinsProtein Tyrosine PhosphatasesReceptors, Chimeric AntigenReceptors, ImmunologicROBO1 protein, humanRoundabout Proteins

Identifiers

PMID39095594

What OpenQuestion holds

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Registered trials

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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.