Evidence map›Paper›PMID 39366383›Full record

ArticleCell reports. Medicine2024

De novo GTP synthesis is a metabolic vulnerability for the interception of brain metastases.

Agata M Kieliszek, Daniel Mobilio, Blessing I Bassey-Archibong, Jarrod W Johnson, Mathew L Piotrowski, Elvin D de Araujo, Abootaleb Sedighi, Nikoo Aghaei, Laura Escudero, Patrick Ang and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 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
–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

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Coupling proteostasis andTheranostics · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025
    Review
  10. 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

24 authors.

Agata M KieliszekCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Daniel MobilioCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Blessing I Bassey-ArchibongCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Jarrod W JohnsonDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Mathew L PiotrowskiDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Elvin D de AraujoCentre for Medicinal Chemistry, University of Toronto Mississauga, Mississauga, ON, Canada.
Abootaleb SedighiCentre for Medicinal Chemistry, University of Toronto Mississauga, Mississauga, ON, Canada.
Nikoo AghaeiCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Laura EscuderoCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Patrick AngCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada.
William D GwynneCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Cunjie ZhangTerrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Andrew QuaileTerrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Dillon McKennaCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Minomi SubapandithaDepartment of Surgery, McMaster University, Hamilton, ON, Canada.
Tomas TokarKrembil Research Institute, University Health Network, Toronto, ON, Canada.
Muhammad Vaseem ShaikhCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Kui ZhaiCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Shawn C ChafeCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Patrick T GunningCentre for Medicinal Chemistry, University of Toronto Mississauga, Mississauga, ON, Canada.
J Rafael Montenegro-BurkeTerrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Chitra VenugopalCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada.
Jakob MagolanDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Sheila K SinghCentre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada. Electronic address: ssingh@mcmaster.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Patients with brain metastases (BM) face a 90% mortality rate within one year of diagnosis and the current standard of care is palliative. Targeting BM-initiating cells (BMICs) is a feasible strategy to treat BM, but druggable targets are limited. Here, we apply Connectivity Map analysis to lung-, breast-, and melanoma-pre-metastatic BMIC gene expression signatures and identify inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo GTP synthesis pathway, as a target for BM. We show that pharmacological and genetic perturbation of IMPDH attenuates BMIC proliferation in vitro and the formation of BM in vivo. Metabolomic analyses and CRISPR knockout studies confirm that de novo GTP synthesis is a potent metabolic vulnerability in BM. Overall, our work employs a phenotype-guided therapeutic strategy to uncover IMPDH as a relevant target for attenuating BM outgrowth, which may provide an alternative treatment strategy for patients who are otherwise limited to palliation.

Indexed as

Brain NeoplasmsGuanosine TriphosphateIMP DehydrogenaseAnimalsCell Line, TumorCell ProliferationFemaleHumansMiceGuanosine TriphosphateIMP Dehydrogenasebrain metastasescancer stem cellsGTP synthesisIMPDH

Identifiers

PMID39366383
PMCPMC11513854

What OpenQuestion holds

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LicenceCC BY
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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.