Key result
L-carnitine may mitigate TKI-induced cardiotoxicity driven by mitochondrial dysfunction and inflammation.
Why the study?
Tyrosine kinase inhibitors are associated with cardiovascular toxicity, and metabolomics offers a framework to identify early biochemical disruptions preceding clinical manifestations and to formulate mechanistic intervention strategies.
Does metabolomic profiling identify early biochemical disruptions in TKI-induced cardiovascular toxicity?
Does metabolomic profiling identify early biochemical disruptions in TKI-induced cardiovascular toxicity?
Metabolomic profiling identifies key biochemical disruptions in TKI-induced cardiotoxicity, offering potential mechanistic biomarkers for early detection and targeted prevention.
Supports metabolomic biomarkers for early TKI cardiotoxicity detection; extends rationale for L-carnitine prevention trials.
Background: Tyrosine 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. Methods: We 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. Conclusions: Metabolomic 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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Singh et al. (2026) studied this question. Tyrosine kinase inhibitors induce cardiotoxicity through mitochondrial dysfunction, disrupted nitric oxide signaling, and inflammation, which L-carnitine may help mitigate.
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