Article in European heart journal, 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.
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
21 authors.
Kai ZhangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0009-0009-7164-9556
Alyssa AyalaDivision of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
Ignacio Norambuena-SotoDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0002-2676-2674
Vertica AgnihotriDivision of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0003-2068-8773
Tao ShuIntegrative Genomics Shared Resource, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Christian NenningerDivision of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0009-0008-7580-5328
Yin WangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0002-2508-7881
Brittany EchevarriaDivision of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0009-0000-4099-3041
Joel AboagyeDepartment of Biomedical Engineering, University of North Texas, Denton, TX 76205, USA.
Katie HuangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
Jenaro Espitia-CorredorDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0003-2454-9746
Xiwei WuDepartment of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Zhen B ChenDepartment of Diabetes Complications and Metabolism, Arthur Riggs Diabetes Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.ORCID 0000-0002-3291-1090
Yingfeng DengDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
J Jefferson P PerryDepartment of Molecular Diagnostics and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.ORCID 0000-0001-9889-3502
Dan J RazDepartment of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA.
Huaxiao YangDepartment of Biomedical Engineering, University of North Texas, Denton, TX 76205, USA.ORCID 0000-0001-9335-8201
Paul ChengDivision of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-3429-2702
Guosheng FuDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.ORCID 0000-0001-7027-0717
Zhao V WangDepartment of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0002-9904-9538
June-Wha RheeDivision of Cardiology, Department of Medicine, Beckman Research Institute, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.ORCID 0000-0002-7044-2985
Funding
American Diabetes Association 7-20-IBS-218American Heart Association 19IPLOI34760325American Heart Association 947398
6 · The paper itself
Abstract
BACKGROUND AND
aimsOsimertinib is a third-generation tyrosine kinase inhibitor targeting activating mutations of epidermal growth factor receptor with remarkable therapeutic efficacy against non-small cell lung carcinoma. However, its use has been limited by associated cardiotoxicity, primarily with heart failure. Herein, this study aims to better understand the mechanisms underlying osimertinib cardiotoxicity and explore cardioprotective strategies.
methodsThis study leverages an in vitro model of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and a clinically relevant in vivo mouse model of osimertinib cardiotoxicity by co-employing transverse aortic constriction to mimic haemodynamic stress in cancer patients.
resultsOsimertinib treatment leads to significant contractile dysfunction in mice without cell death, inflammation, or fibrosis. By leveraging single-nucleus RNA sequencing of mouse heart tissues and in vitro assays of human iPSC-CMs, the study reveals significant downregulation of MYLK3 and a subsequent decrease in MYL2 phosphorylation with marked sarcomere disarray as the main mechanism of osimertinib cardiotoxicity. GATA4 is further identified as a putative target of osimertinib, connecting its decreased phosphorylation to repressed MYLK3 transcription. The reversibility of osimertinib-induced cardiac dysfunction upon discontinuation of osimertinib treatment supports the hypothesis that transient sarcomere disruption, rather than permanent cellular damage, serves as the key underlying mechanism. Finally, the myosin activator omecamtiv is shown to be effective in preventing osimertinib cardiotoxicity.
conclusionsThese findings suggest that osimertinib causes reversible cardiac dysfunction by disrupting MYL2 phosphorylation via GATA4 dephosphorylation-mediated suppression of MYLK3 and highlight the potential of myosin activation as a preventive or rescue strategy for osimertinib cardiotoxicity.
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.
Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis. · full record | OpenQuestion