ArticleCardiovascular research2015
Oestrogen enhances cardiotoxicity induced by Sunitinib by regulation of drug transport and metabolism.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 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
- Sex-specific angiogenic responses in endothelial cells-role of the pluripotency factor OCT4.Angiogenesis · 2025Article
- Translational regulation of SND1 governs endothelial homeostasis during stress.The Journal of clinical investigation · 2025Article
- Rivaroxaban Ameliorates Sunitinib-Induced Injury of Cardiomyocytes via Repressing MAPK Signaling Pathway.Cardiovascular therapeutics · 2025Article
- A comprehensive review on the effects of sex hormones on chemotherapy-induced cardiotoxicity: are they lucrative or unprofitable?Cardio-oncology (London, England) · 2024Review
- In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation.Journal of cardiovascular translational research · 2022Review
- Sex-related differential susceptibility to ponatinib cardiotoxicity and differential modulation of the Notch1 signalling pathway in a murine model.Journal of cellular and molecular medicine · 2022Article
- A framework for developing sex-specific engineered heart models.Nature reviews. Materials · 2022Review
- Sex-Specific Classification of Drug-Induced Torsade de Pointes Susceptibility Using Cardiac Simulations and Machine Learning.Clinical pharmacology and therapeutics · 2021Article
- Computational model of cardiomyocyte apoptosis identifies mechanisms of tyrosine kinase inhibitor-induced cardiotoxicity.Journal of molecular and cellular cardiology · 2021Article
- CYP1B1 as a therapeutic target in cardio-oncology.Clinical science (London, England : 1979) · 2020Article
- 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.Journal of the American Heart Association · 2017Article
- A Novel Positron Emission Tomography (PET) Approach to Monitor Cardiac Metabolic Pathway Remodeling in Response to Sunitinib Malate.PloS one · 2017Article
- Testosterone Antagonizes Doxorubicin-Induced Senescence of Cardiomyocytes.Journal of the American Heart Association · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
aimsTo define the molecular mechanisms of cardiotoxicity induced by Sunitinib and to identify the role of biological sex in modulating toxicity. METHODS AND
resultsExposure of isolated cardiomyocytes to plasma-relevant concentrations of Sunitinib and other tyrosine kinase inhibitors produces a broad spectrum of abnormalities and cell death via apoptosis downstream of sexually dimorphic kinase inhibition. Phosphorylation of protein kinase C and phospholipase γ abrogates these effects for most tyrosine kinase inhibitors tested. Female sex and estradiol cause increased cardiotoxicity, which is mediated by reduced expression of a drug efflux transporter and a metabolic enzyme. Female but not male mice exposed to a 28-day course of oral Sunitinib exhibit similar abnormalities as well as functional deficits and their hearts exhibit differential expression of genes responsible for transport and metabolism of Sunitinib.
conclusionWe identify the specific pathways affected by tyrosine kinase inhibitors in mammalian cardiomyocytes, interactions with biological sex, and a role for oestrogen in modulating drug efflux and metabolism. These findings represent a critical step toward reducing the incidence of cardiotoxicity with tyrosine kinase inhibitor chemotherapeutics.
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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.