ArticleJournal of the American Heart Association2017
Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity From Combined Signal Transducer and Activator of Transcription and Epidermal Growth Factor Receptor Inhibition.
Article in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled 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.
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
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 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
- Major Adverse Cardiovascular Events in Angiogenesis Inhibitor-Based Cancer Therapy: A Systematic Review and Meta-Analysis.Journal of the American Heart Association · 2025Pooled it
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- Astragaloside IV Reduces Sorafenib-Induced Cardiotoxicity by Inhibiting Apoptosis Through the STAT3/HIF-1α/Bcl-2 Signaling Pathway.International journal of molecular sciences · 2026Article
- The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.Translational cancer research · 2026Review
- Signals of pericardial and myocardial events associated with antiangiogenic drugs: a disproportionality analysis on FAERSEuropean journal of clinical pharmacology · 2026Article
- Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective.Science translational medicine · 2025Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 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
- Hypertension toxicity of VEGFR-TKIs in cancer treatment: incidence, mechanisms, and management strategies.Archives of toxicology · 2025Review
- Is There a Mitochondrial Protection via Remote Ischemic Conditioning in Settings of Anticancer Therapy Cardiotoxicity?Current heart failure reports · 2024Review
- Social Determinants of Health in Cardio-Oncology: Multi-Level Strategies to Overcome Disparities in Care:JACC. CardioOncology · 2024Review
- Erlotinib suppresses tumorigenesis in a mouse model of colitis-associated cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond.Frontiers in pharmacology · 2024Review
- Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.Signal transduction and targeted therapy · 2023Review
- EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation.JCI insight · 2023Article
- Emerging mitochondrial signaling mechanisms in cardio-oncology: beyond oxidative stress.American journal of physiology. Heart and circulatory physiology · 2022Review
- Autophagic degradation of CCN2 (cellular communication network factor 2) causes cardiotoxicity of sunitinib.Autophagy · 2022Article
- Cardiovascular Risks with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors and Monoclonal Antibody Therapy.Current oncology reports · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMost novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND
resultsWe administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor beads coupled with mass spectrometry. We found unexpectedly broad molecular effects of all 3 kinase inhibitors, suggesting that target kinase selectivity does not define either the molecular response or the potential for cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte culture, we also show that the cardiosafety of erlotinib treatment may result from upregulation of the cardioprotective signal transducer and activator of transcription 3 pathway, as co-treatment with erlotinib and a signal transducer and activator of transcription inhibitor decreases cardiac contractile function and cardiomyocyte fatty acid oxidation.
conclusionsCollectively our findings indicate that preclinical kinome and transcriptome profiling may predict the cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed therapeutic strategy of combined signal transducer and activator of transcription/epidermal growth factor receptor inhibition for cancer treatment.
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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.