ArticleJournal of molecular and cellular cardiology2021
Computational model of cardiomyocyte apoptosis identifies mechanisms of tyrosine kinase inhibitor-induced cardiotoxicity.
Article in Journal of molecular and cellular cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Systems modelling of mitochondrial dynamics in different exercise regimes.The Journal of physiology · 2026Article
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- SIRT7 upregulation protects against TKI-induced cardiotoxicity by inhibiting MCU-mediated mitochondrial calcium overload.Frontiers in pharmacology · 2026Article
- Deciphering Cancer Therapy-Induced Cardiotoxicity in the Era of Spatial and Multi-Omics from Systemic Mechanisms toJournal of Cancer · 2026Review
- A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.Cardiovascular drugs and therapy · 2025Review
- 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
- Logic-based modeling of biological networks with Netflux.PLoS computational biology · 2025Article
- Modeling cardiomyocyte signaling and metabolism predicts genotype-to-phenotype mechanisms in hypertrophic cardiomyopathy.Computers in biology and medicine · 2024Article
- Astragaloside IV attenuates sunitinib-associated cardiotoxicity by inhibiting COUP-TFII.Heliyon · 2024Article
- Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.Drug design, development and therapy · 2024Review
- Integrating Metabolomics, Histopathology, and Cardiac Marker Analysis to Assess Valsartan's Efficacy in Mitigating Dasatinib-Induced Cardiac Toxicity in Sprague-Dawley Rats.Drug design, development and therapy · 2024Article
- Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond.Frontiers in pharmacology · 2024Review
- Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact.Scientific reports · 2023Article
- Low-intensity pulsed ultrasound of different intensities differently affects myocardial ischemia/reperfusion injury by modulating cardiac oxidative stress and inflammatory reaction.Frontiers in immunology · 2023Article
- Structural and functional diversity of mitochondria in vestibular/cochlear hair cells and vestibular calyx afferents.Hearing research · 2022Review
- Reengineering Ponatinib to Minimize Cardiovascular Toxicity.Cancer research · 2022Article
- Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity.Heart failure clinics · 2022Review
- Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation.Pharmaceutics · 2022Review
- Friend or foe? Unraveling the complex roles of protein tyrosine phosphatases in cardiac disease and development.Cellular signalling · 2022Review
- Unveiling the Cardiotoxicity Conundrum: Navigating the Seas of Tyrosine Kinase Inhibitor Therapies.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Despite clinical observations of cardiotoxicity among cancer patients treated with tyrosine kinase inhibitors (TKIs), the molecular mechanisms by which these drugs affect the heart remain largely unknown. Mechanistic understanding of TKI-induced cardiotoxicity has been limited in part due to the complexity of tyrosine kinase signaling pathways and the multi-targeted nature of many of these drugs. TKI treatment has been associated with reactive oxygen species generation, mitochondrial dysfunction, and apoptosis in cardiomyocytes. To gain insight into the mechanisms mediating TKI-induced cardiotoxicity, this study constructs and validates a computational model of cardiomyocyte apoptosis, integrating intrinsic apoptotic and tyrosine kinase signaling pathways. The model predicts high levels of apoptosis in response to sorafenib, sunitinib, ponatinib, trastuzumab, and gefitinib, and lower levels of apoptosis in response to nilotinib and erlotinib, with the highest level of apoptosis induced by sorafenib. Knockdown simulations identified AP1, ASK1, JNK, MEK47, p53, and ROS as positive functional regulators of sorafenib-induced apoptosis of cardiomyocytes. Overexpression simulations identified Akt, IGF1, PDK1, and PI3K among the negative functional regulators of sorafenib-induced cardiomyocyte apoptosis. A combinatorial screen of the positive and negative regulators of sorafenib-induced apoptosis revealed ROS knockdown coupled with overexpression of FLT3, FGFR, PDGFR, VEGFR, or KIT as a particularly potent combination in reducing sorafenib-induced apoptosis. Network simulations of combinatorial treatment with sorafenib and the antioxidant N-acetyl cysteine (NAC) suggest that NAC may protect cardiomyocytes from sorafenib-induced apoptosis.
Indexed as
Identifiers
What Socratic 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 Socratic graph.