Metabolomic Profiling and the Identification of Predictive Biomarkers for Chemotherapy-Induced Cardiotoxicity

Chemotherapy-induced cardiotoxicity (CIC) remains a major complication of cancer treatment, particularly with anthracyclines and HER2-targeted therapies. This review evaluates metabolomic biomarkers predictive of cardiac dysfunction, including dysregulated lipid species (ceramides, acylcarnitines), energy metabolites (ATP, NAD+), and oxidative stress markers (malondialdehyde). Advances in high-resolution mass spectrometry and nuclear magnetic resonance (NMR) have enabled the identification of early metabolic signatures, such as plasma ceramide d18:1/24:1 (AUC 0.88) and depleted branched-chain amino acids (BCAAs), which precede echocardiographic changes by 3–6 months. We discuss the integration of metabolomics with proteomic and genomic data to refine risk stratification, alongside challenges in biomarker validation and clinical implementation. Future directions emphasize real-time metabolomic monitoring and targeted metabolic interventions to mitigate CIC while preserving oncological efficacy.