ArticleScientific reports2018
The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Cardiotoxicity of Targeted Therapies in Hematologic Malignancies: From Molecular Mechanisms to Clinical Management.Current treatment options in oncology · 2026Review
- Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity.Metabolites · 2026Review
- Cancer treatment-related cardiotoxicity, molecular mechanism, challenges, and research trends.Discover oncology · 2026Review
- 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
- A fatal case of cabozantinib-induced cardiomyopathy.Future cardiology · 2024Article
- Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.Signal transduction and targeted therapy · 2023Review
- CaInternational journal of molecular sciences · 2023Article
- Merits of hiPSC-Derived Cardiomyocytes for In Vitro Research and Testing Drug Toxicity.Biomedicines · 2022Article
- Kir2.1 dysfunction at the sarcolemma and the sarcoplasmic reticulum causes arrhythmias in a mouse model of Andersen-Tawil syndrome type 1.Nature cardiovascular research · 2022Article
- Acute heart failure following the initiation of cabozantinib, a multikinase inhibitor: A case report.Journal of cardiology cases · 2022Article
- 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
- Comparative Analysis of the Cytotoxic Effect of a Complex of Selenium Nanoparticles Doped with Sorafenib, "Naked" Selenium Nanoparticles, and Sorafenib on Human Hepatocyte Carcinoma HepG2 Cells.International journal of molecular sciences · 2022Article
- Treatment effects of the EGFR pathway drugs on head and neck cancer stem cells.American journal of cancer research · 2022Article
- Hesperetin mitigates sorafenib-induced cardiotoxicity in mice through inhibition of the TLR4/NLRP3 signaling pathway.PloS one · 2022Article
- Structural and Electrophysiological Changes in a Model of Cardiotoxicity Induced by Anthracycline Combined With Trastuzumab.Frontiers in physiology · 2021Article
- Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity.Advanced healthcare materials · 2020Review
- Sorafenib- Taurine Combination Model for Hepatocellular Carcinoma Cells: Immunological Aspects.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients.Cardiac failure review · 2019Review
- Downregulation of miR-146a Contributes to Cardiac Dysfunction Induced by the Tyrosine Kinase Inhibitor Sunitinib.Frontiers in pharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: -25 ± 4%, 10 µM: -29 ± 7%, 30 µM: -43 ± 12%, p < 0.01), reduced peak cytosolic calcium concentrations in isolated cardiomyocytes (10 µM: 52 ± 8.1% of baseline, p < 0.001), and slowed cytosolic calcium removal kinetics (RT50, RT10, Tau, p < 0.05). Beta-adrenergic stimulation induced augmentation of calcium transient (CaT) amplitude was attenuated in sorafenib-treated cells (2.7 ± 0.3-fold vs. 3.6 ± 0.2-fold in controls, p < 0.001). Sarcoplasmic reticulum (SR) calcium content was reduced to 67 ± 4% (p < 0.01), and SR calcium re-uptake slowed (p < 0.05). Sorafenib significantly reduced serine 16 phosphorylation of phospholamban (PLN, p < 0.05), while PLN threonine 17 and CaMKII (T286) phosphorylation were not altered. Our data demonstrate that sorafenib acutely impairs cardiac contractility by reducing S16 PLN phosphorylation, leading to reduced SR calcium content, CaT amplitude, and slowed cytosolic calcium removal. These results indicate myocyte intrinsic cardiotoxicity irrespective of effects on the vasculature and chronic cardiac remodeling.
Indexed as
Identifiers
What OpenQuestion holds
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.