Cancer treatment-related cardiotoxicity, molecular mechanism, challenges, and research trends

Cancer treatment-related cardiotoxicity (CTRC) encompasses a spectrum of cardiovascular complications associated with chemotherapy, targeted therapy, and radiotherapy. This review synthesizes recent mechanistic insights to delineate distinct pathological pathways: anthracyclines provoke oxidative mitochondrial damage and disrupt cardiomyocyte iron homeostasis; HER2-targeted therapies inhibit the PI3K-Akt survival pathway, compromising contractile function and calcium regulation; tyrosine kinase inhibitors impair VEGF and PDGF signaling, inducing endothelial dysfunction and microvascular rarefaction; immune checkpoint inhibitors activate T-cell-mediated myocarditis; and thoracic radiation initiates endothelial inflammation followed by TGF-β–dependent fibrotic remodeling. These mechanism-specific injuries follow a characteristic clinical sequence, with arrhythmias and myocarditis emerging acutely, subclinical contractile dysfunction developing within months, and overt heart failure or vascular stenosis manifesting years post-treatment. We highlight the critical roles of advanced imaging and biomarker-based surveillance in early detection, and underscore evidence-based cardioprotective interventions that maintain anticancer efficacy while mitigating cardiovascular risk.