Evidence map›Paper›PMID 40215978›Full record

ArticleCancer cell2025

Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance.

Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
–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

55 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  18. Role of Ferredoxin 1Cancer pathogenesis and therapy · 2026
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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

26 authors.

Guang LeiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mingchuang SunDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jun ChengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rui YeDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhengze LuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Amber HorbathDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
David HuoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shengrong WuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anagha AlapatiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sadhna AggarwalDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhihao XuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Chao MaoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yuelong YanDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jun YaoDepartment of Molecular and Cellular Oncology, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Qidong LiDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xiong ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hyemin LeeDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Li ZhuangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dadi JiangDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Apar PataerDepartment of Thoracic and Cardiovascular Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jack A RothDepartment of Thoracic and Cardiovascular Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nicholas NavinDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Albert C KoongDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mingjian James YouDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Steven H LinDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: shlin@mdanderson.org.
Boyi GanDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address: bgan@mdanderson.org.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Collin M Blakely · 2017 to 2026
$12.9M
Tumor hypoxia promotes acquired resistance to radiation through ferroptosis inhibitionU54CA274220 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Steven Hsesheng Lin · 2022 to 2026
$8.4M
Studying metabolic stress signaling in renal cancerR01CA181196 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2014 to 2024
$3.4M
Targeting SLC7A11-induced nutrient dependency in cancer: mechanisms and preclinical translationR01CA244144 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2020 to 2024
$2.1M
Targeting ferroptosis in cancer therapyR01CA269646 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Boyi Gan · 2023 to 2026
$2.0M
Targeting ferroptosis in radioresistance in lung cancer: mechanisms and preclinical translationR01CA247992 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GAN, BOYI · 2021 to 2025
$1.9M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA181196NCI NIH HHS R01 CA244144NCI NIH HHS R01 CA247992NCI NIH HHS R01 CA269646NCI NIH HHS U54 CA224081NCI NIH HHS U54 CA274220
6 · The paper itself

Abstract

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the expression of copper-sequestering metallothionein (MT) 1E/X, thereby mitigating cuproptosis and contributing to radioresistance. Copper ionophore treatment sensitizes radioresistant cancer cells and cell line- and patient-derived xenografts to RT by potentiating cuproptosis. Our findings unveil a link between RT and cuproptosis and inform a therapeutic strategy to overcome tumor radioresistance by targeting cuproptosis.

Indexed as

CopperEsophageal NeoplasmsRadiation ToleranceAnimalsApoptosisCell Line, TumorCopper Transporter 1FemaleFerroptosisGene Expression Regulation, NeoplasticGlutathioneHumansMetallothioneinMiceMitochondriaXenograft Model Antitumor AssaysCopperCopper Transporter 1GlutathioneMetallothioneincoppercuproptosismetallothioneinradioresistanceradiotherapy

Identifiers

PMID40215978
PMCPMC12151758

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.