Doxorubicin-Induced Cardiomyopathy: Molecular Mechanisms and Emerging Therapeutic Strategies

Doxorubicin, a potent anthracycline chemotherapeutic agent, is widely used in the treatment of various cancers but is significantly limited by its dose-dependent cardiotoxicity, which can progress to cardiomyopathy and heart failure. Doxorubicin-induced cardiomyopathy is a multifactorial condition involving a complex interplay of molecular and cellular mechanisms, including oxidative stress, mitochondrial dysfunction, apoptosis, autophagy dysregulation, and inflammatory signalling. Reactive oxygen species overproduction and impaired antioxidant defences play a central role in cardiac damage, while mitochondrial injury contributes to bioenergetics failure and cardio myocyte death. Additionally, the activation of pro-inflammatory cytokines and the disruption of calcium homeostasis further exacerbate cardiac dysfunction. Despite advancements in understanding these pathways, clinically effective strategies to prevent or reverse DIC remain limited. Recent research has focused on identifying novel therapeutic targets and cardio protective agents, including natural antioxidants, mitochondrial stabilizers, iron chelators, and pharmacological modulators of autophagy and apoptosis. The development of targeted drug delivery systems and the repurposing of established cardiovascular drugs also offer promising avenues for mitigating doxorubicin-induced cardiac injury. This review provides a comprehensive overview of the current knowledge on the molecular underpinnings of DIC and explores recent advances in therapeutic strategies aimed at preserving cardiac function during and after doxorubicin therapy.