Evidence map›Paper›PMID 41541699›Full record

ArticleiScience2026

Systemic cyst(e)inase administration induces ferroptosis and synergizes with temozolomide in glioblastoma.

Fahim Ahmad, Blair P Rendina, Chixiang Chen, Haoyu Ren, Christine Brantner, Tijana Dukic, Delmar Miles, Jeffrey A Winkles, Graeme F Woodworth, Sarita Bhetawal and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Fahim AhmadDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Blair P RendinaDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Chixiang ChenDepartment of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Haoyu RenDepartment of Mathematics and Statistics, University of Maryland, Baltimore, MD, USA.
Christine BrantnerDepartment of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, MD, USA.
Tijana DukicDepartment of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, MD, USA.
Delmar MilesDepartment of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, MD, USA.
Jeffrey A WinklesDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Graeme F WoodworthDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Sarita BhetawalDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Everett StoneDepartment of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
Eli E BarDepartment of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Funding

In Vivo Fluorescence and Bioluminescence Imager with CTS10OD030430 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI LAPIDUS, RENA · 2021 to 2021
$600k
NIH HHS S10 OD030430
6 · The paper itself

Abstract

Glioblastoma exhibits profound therapeutic resistance, driven by tumor heterogeneity and highly plastic glioma stem cells (GSCs). This study exploits GSC metabolic dependence on cysteine using systemic cyst(e)inase, a cysteine-degrading enzyme. In patient-derived GSCs and orthotopic xenograft models, cyst(e)inase potently inhibited GSC proliferation and extended animal survival by inducing ferroptosis. Mechanistically, cyst(e)inase triggered elevated reactive oxygen species (ROS), glutathione (GSH) depletion, and significant lipid peroxidation. Crucially, these effects were reversed by N-acetylcysteine (NAC), and lipid peroxidation was abrogated by the iron chelator deferoxamine (DFX), unequivocally confirming iron-dependent ferroptosis. Characteristic mitochondrial morphological changes further validated ferroptosis induction. Acyl-CoA synthetase long-chain family member-4 (ACSL4) was identified as essential for this process. Critically, cyst(e)inase synergized with temozolomide (TMZ), markedly enhancing its anti-tumor efficacy and prolonging survival, even in TMZ-resistant xenografts. These findings establish cysteine metabolism as a promising therapeutic target and position cyst(e)inase, especially with TMZ, as a potent strategy to overcome GBM resistance.

Indexed as

microenvironment

Identifiers

PMID41541699
PMCPMC12799779

What OpenQuestion 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 OpenQuestion graph.