Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies

Doxorubicin (DOX) is a widely used anthracycline chemotherapeutic agent; however, its clinical application is limited by dose-dependent cardiotoxicity, which can result in progressive cardiac dysfunction and heart failure. Increasing evidence indicates that DOX-induced cardiotoxicity is closely associated with premature cardiac senescence, a pathological process distinct from physiological cardiac aging. DOX induces senescence-associated alterations in multiple cardiac cell populations, disrupting cardiac homeostasis and contributing to pathological remodeling. In this review, we summarize current advances in DOX-induced cardiac senescence, focusing on the contributions of different cardiac cell types, the underlying molecular mechanisms, and emerging therapeutic strategies. We further discuss the challenges and future perspectives for developing effective interventions that alleviate cardiac senescence while preserving the anticancer efficacy of DOX. Understanding the mechanisms driving DOX-induced cardiac senescence may provide new opportunities to develop effective cardioprotective strategies and improve long-term cardiac outcomes after chemotherapy.