Evidence map›Paper›PMID 41942611›Full record

ArticleBritish journal of cancer2026

Arachidonate lipoxygenase 5 metabolism axis promoting ferroptosis: a potential druggable target for doxorubicin-induced cardiomyopathy.

Lu Chen, Xingang Sun, Han Zhang, Xuan Zhang, Mairedan Muhetarijiang, Zuoshi Wen, Chenxi Li, Mengjia Chen, Zhangquan Ying, Shuai Yuan and 2 more

Abstract read
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In one paragraph

Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Lu Chen *Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Xingang Sun *Department of Cardiology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang Province, China.
Han ZhangDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Xuan ZhangDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Mairedan MuhetarijiangDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Zuoshi WenDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Chenxi LiDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Mengjia ChenDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Zhangquan YingDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Shuai YuanDepartment of Echocardiography and Vascular Ultrasound Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Liangrong ZhengDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. 1191066@zju.edu.cn.
Ting ChenDepartment of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. ct010151452@zju.edu.cn.ORCID http://orcid.org/0000-0002-9723-9020

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDoxorubicin (Dox) is a widely-used anthracycline drug for various cancers, but its clinical application is limited due to cardiotoxicity. Targeting ferroptosis is a new and effective strategy for treating Dox-induced cardiomyopathy (DIC). The arachidonate lipoxygenase 5 (ALOX5) metabolism axis is closely linked to ferroptosis, but its role in DIC remains unknown.

methodsIn vivo and in vitro DIC models were established to investigate the role of the ALOX5 metabolism axis in DIC and to clarify the underlying mechanism using genetic and pharmacological approaches.

resultsOur findings revealed that ALOX5 and 5-hydroxyicosatetraenoic acid (5-HETE) levels were increased in DIC. Overexpression of Alox5 exacerbated Dox-induced cardiac dysfunction and myocardial injury, whereas pharmacological inhibition and genetic knockdown of ALOX5 alleviated these effects by modulating ferroptosis. Mechanistically, elevated ALOX5 catalyzed the metabolism of arachidonic acid to generate 5-HETE, which facilitated NRF2 ubiquitination-dependent degradation via PI3K/AKT/GSK-3β signaling, thereby contributing to cardiomyocyte ferroptosis.

conclusionsThis study suggests that targeting cardiomyocyte ferroptosis mediated by the ALOX5 metabolism axis may represent a therapeutic strategy for DIC.

Indexed as

Arachidonate 5-LipoxygenaseCardiomyopathiesDoxorubicinFerroptosisAnimalsAntibiotics, AntineoplasticGlycogen Synthase Kinase 3 betaHumansHydroxyeicosatetraenoic AcidsMaleMiceMyocytes, CardiacNF-E2-Related Factor 2Proto-Oncogene Proteins c-aktSignal Transduction5-hydroxy-6,8,11,14-eicosatetraenoic acidAntibiotics, AntineoplasticArachidonate 5-LipoxygenaseDoxorubicinGlycogen Synthase Kinase 3 betaHydroxyeicosatetraenoic AcidsNF-E2-Related Factor 2Proto-Oncogene Proteins c-akt

Identifiers

PMID41942611
PMCPMC13183924

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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.