ArticleCell systems2019
Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming.
Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Integrated Electrophysiological and Optical Analysis of Human iPSC-Derived Cardiomyocytes Using Transparent ITO Microelectrode Chip.International journal of stem cells · 2026Article
- Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity.Metabolites · 2026Review
- Cardiovascular Disease Meets Cancer: Exploring the Epidemiology in China and Homotherapy Targeting Intersectional Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Bridging the Gap Between hiPSC-CMs Cardiotoxicity Assessment and Clinical LVEF Decline Risk: A Case Study of 21 Tyrosine Kinase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pathway-Based Similarity Measurement to Quantify Transcriptomics Similarity Between Human Tissues and Preclinical Models.Clinical pharmacology and therapeutics · 2025Article
- Cardiotoxicity of Chemotherapy: A Multi-OMIC Perspective.Journal of xenobiotics · 2025Review
- Clinical trials in-a-dish for cardiovascular medicine.European heart journal · 2024Review
- Sorafenib induces cachexia by impeding transcriptional signaling of the SET1/MLL complex on muscle-specific genes.iScience · 2024Article
- Multiscale mapping of transcriptomic signatures for cardiotoxic drugs.Nature communications · 2024Article
- Informing Hazard Identification and Risk Characterization of Environmental Chemicals by Combining Transcriptomic and Functional Data from Human-Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.Chemical research in toxicology · 2024Article
- From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.Pharmaceutics · 2024Review
- Guidelines for Manufacturing and Application of Organoids: Heart.International journal of stem cells · 2024Article
- Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.Science China. Life sciences · 2024Article
- Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.Drug design, development and therapy · 2024Review
- Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.Signal transduction and targeted therapy · 2023Review
- Circulating biomarkers for management of cancer therapeutics-related cardiac dysfunction.Cardiovascular research · 2023Review
- iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation.Scientific reports · 2023Article
- Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes.BMC medicine · 2023Article
- Ectopic expression of SARS-CoV-2 S and ORF-9B proteins alters metabolic profiles and impairs contractile function in cardiomyocytes.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Tyrosine kinase inhibitors (TKIs) are widely used to treat solid tumors but can be cardiotoxic. The molecular basis for this toxicity and its relationship to therapeutic mechanisms remain unclear; we therefore undertook a systems-level analysis of human cardiomyocytes (CMs) exposed to four TKIs. CMs differentiated from human induced pluripotent stem cells (hiPSCs) were exposed to sunitinib, sorafenib, lapatinib, or erlotinib, and responses were assessed by functional assays, microscopy, RNA sequencing, and mass spectrometry (GEO: GSE114686; PRIDE: PXD012043). TKIs have diverse effects on hiPSC-CMs distinct from inhibition of tyrosine-kinase-mediated signal transduction; cardiac metabolism is particularly sensitive. Following sorafenib treatment, oxidative phosphorylation is downregulated, resulting in a profound defect in mitochondrial energetics. Cells adapt by upregulating aerobic glycolysis. Adaptation makes cells less acutely sensitive to sorafenib but may have long-term negative consequences. Thus, CMs exhibit adaptive responses to anti-cancer drugs conceptually similar to those previously shown in tumors to mediate drug resistance.
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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.