ReviewMetabolites2026
Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity.
Review in Metabolites, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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Who cites it
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Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTyrosine kinase inhibitors (TKIs) have transformed cancer therapy; however, they are associated with cardiovascular toxicity. Metabolomics provides a comprehensive framework for identifying early biochemical disruptions that precede clinical manifestations and for formulating mechanism-based intervention strategies.
methodsWe conducted a narrative synthesis of published preclinical and translational studies on TKI cardiotoxicity, focusing on untargeted and targeted metabolomic findings and complementary proteomic and transcriptomic data. Functional validation was performed using rodent and cellular models. Mechanistic themes were identified, and implications for biomarker panels, multi-omic integration, and metabolomics-guided interventions were proposed.
conclusionsMetabolomic analyses of various TKIs identified convergent signatures along three interconnected axes: (1) mitochondrial bioenergetic dysfunction characterized by impaired long-chain fatty acid oxidation and adenylate depletion; (2) disruption of endothelial nitric oxide signaling with redox imbalance, including increased nitrotyrosine, Nox activation, and eNOS uncoupling; and (3) an inflammatory metabolic profile marked by elevated branched-chain and aromatic amino acids, creatine, and osmolytes. Rodent models of sunitinib and sorafenib replicate these signatures and demonstrate histological injury, contractile dysfunction, and fibrosis. Preclinical intervention data, particularly restoration of myocardial carnitine, AMPK signaling, and fatty acid oxidation by L-carnitine, provide proof of concept for metabolomics-guided cardioprotection. Metabolomics can identify mechanistic biomarkers that facilitate the early detection, risk stratification, and targeted prevention of TKI-induced cardiovascular injury. Translation into precision cardio-oncology requires prospective validation, standardized assays, and biomarker-driven interventional trials.
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