Emerging Targets and Treatments for Doxorubicin-Induced Cardiac Inflammation

Doxorubicin (DOX) is one of the most effective and widely used anthracycline chemotherapeutic agents, yet its clinical utility is severely limited by cumulative, dose-dependent cardiotoxicity. Currently, clinical management of DOX-induced cardiotoxicity is largely limited to dose adjustment, cardiac monitoring, and nonspecific cardioprotective agents, underscoring the lack of targeted anti-inflammatory strategies in current practice. A growing body of evidence indicates that inflammation is a central driver of DOX-induced cardiotoxicity, synergistically exacerbating oxidative stress, mitochondrial dysfunction, and cardiomyocyte death. These pathological processes not only compromise myocardial contractility, but also accelerate adverse cardiac remodeling, ultimately increasing the risk of heart failure in cancer survivors. Over the past decade, the discovery of non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), and extracellular vesicles such as exosomes has reshaped our understanding of the molecular regulation of cardiac inflammation. These molecules act as crucial modulators of intercellular communication and inflammatory signaling, influencing key pathways such as those involving nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and apoptosis-related cascades. Experimental studies have demonstrated that specific miRNAs and circRNAs suppress the production of inflammatory cytokines, reduce oxidative damage, and enhance survival in DOX-exposed cardiomyocytes and animal models. Similarly, exosome-mediated delivery of protective RNAs or proteins has emerged as a promising approach to mitigate DOX-induced myocardial injury. This review amasses current evidence on the anti-inflammatory functions of miRNAs, circRNAs, and exosomes in DOX-induced cardiac inflammation, highlighting their mechanistic roles, therapeutic potential, and the challenges that must be addressed to move these strategies toward clinical application.