ArticleCirculation research2014
Sorafenib cardiotoxicity increases mortality after myocardial infarction.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Evaluating the use of rodents as in vitro, in vivo and ex vivo experimental models for the assessment of tyrosine kinase inhibitor-induced cardiotoxicity: a systematic review.Archives of toxicology · 2025Pooled it
- Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity.Metabolites · 2026Review
- A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.Cardiovascular drugs and therapy · 2025Review
- Maresin1 Alleviates Ischemia Reperfusion Injury After Lung Transplantation by Inhibiting Ferroptosis via the PKA-Hippo-YAP Signaling Pathway.Biomedicines · 2025Article
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Sorafenib induces cachexia by impeding transcriptional signaling of the SET1/MLL complex on muscle-specific genes.iScience · 2024Article
- The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice.Apoptosis : an international journal on programmed cell death · 2024Article
- Ferroptosis inhibitor alleviates sorafenib-induced cardiotoxicity by attenuating KLF11-mediated FSP1-dependent ferroptosis.International journal of biological sciences · 2024Article
- Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.Drug design, development and therapy · 2024Review
- Cardiovascular Toxicity Induced by Vascular Endothelial Growth Factor Inhibitors.Life (Basel, Switzerland) · 2023Review
- Cardio-oncology in Austria: cardiotoxicity and surveillance of anti-cancer therapies : Position paper of the Heart Failure Working Group of the Austrian Society of Cardiology.Wiener klinische Wochenschrift · 2022Article
- Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic RatioJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Article
- Receptor tyrosine kinase inhibitors negatively impact on pro-reparative characteristics of human cardiac progenitor cells.Scientific reports · 2022Article
- Modeling Nonischemic Genetic Cardiomyopathies Using Induced Pluripotent Stem Cells.Current cardiology reports · 2022Review
- Management of Acute Coronary Syndrome in Cancer Patients: It's High Time We Dealt with It.Journal of clinical medicine · 2022Review
- Harnessing RKIP to Combat Heart Disease and Cancer.Cancers · 2022Review
- A Concomitant Cancer Diagnosis Is Associated With Poor Cardiovascular Outcomes Among Acute Myocardial Infarction Patients.Frontiers in cardiovascular medicine · 2022Article
- Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathwayTheranostics · 2022Article
- Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases.Cell death discovery · 2021Review
- Repurposing Nintedanib for pathological cardiac remodeling and dysfunction.Pharmacological research · 2021Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
rationaleSorafenib is an effective treatment for renal cell carcinoma, but recent clinical reports have documented its cardiotoxicity through an unknown mechanism.
objectiveDetermining the mechanism of sorafenib-mediated cardiotoxicity. METHODS AND
resultsMice treated with sorafenib or vehicle for 3 weeks underwent induced myocardial infarction (MI) after 1 week of treatment. Sorafenib markedly decreased 2-week survival relative to vehicle-treated controls, but echocardiography at 1 and 2 weeks post MI detected no differences in cardiac function. Sorafenib-treated hearts had significantly smaller diastolic and systolic volumes and reduced heart weights. High doses of sorafenib induced necrotic death of isolated myocytes in vitro, but lower doses did not induce myocyte death or affect inotropy. Histological analysis documented increased myocyte cross-sectional area despite smaller heart sizes after sorafenib treatment, further suggesting myocyte loss. Sorafenib caused apoptotic cell death of cardiac- and bone-derived c-kit+ stem cells in vitro and decreased the number of BrdU+ (5-bromo-2'-deoxyuridine+) myocytes detected at the infarct border zone in fixed tissues. Sorafenib had no effect on infarct size, fibrosis, or post-MI neovascularization. When sorafenib-treated animals received metoprolol treatment post MI, the sorafenib-induced increase in post-MI mortality was eliminated, cardiac function was improved, and myocyte loss was ameliorated.
conclusionsSorafenib cardiotoxicity results from myocyte necrosis rather than from any direct effect on myocyte function. Surviving myocytes undergo pathological hypertrophy. Inhibition of c-kit+ stem cell proliferation by inducing apoptosis exacerbates damage by decreasing endogenous cardiac repair. In the setting of MI, which also causes large-scale cell loss, sorafenib cardiotoxicity dramatically increases mortality.
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Registered trials
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.