Cellular crosstalk in doxorubicin-induced cardiotoxicity: underlying mechanisms and therapeutic strategies

Multicellular organisms rely on different forms of intercellular communication to adapt to changes in both internal and external environments and to maintain homeostasis. Doxorubicin-induced cardiotoxicity is frequently linked to dysregulation of intercellular communication. This process involves complex crosstalk between cardiomyocytes and non-cardiomyocytes (fibroblasts, endothelial cells, immune cells and cardiac progenitor cells). However, research into the role of non-cardiomyocyte-mediated interactions in this pathological context remains at an early stage. Despite limited clinical evidence, participants in the crosstalk between these involved cardiac cell populations have emerged as highly promising therapeutic targets, aiming to reduce the risk of doxorubicin-induced cardiotoxicity by maintaining precise intercellular interactions or blocking pathological crosstalk signals. This review seeks to advance the comprehension of the pathological mechanisms underlying doxorubicin-induced cardiotoxicity from an unprecedented perspective of cellular crosstalk and to establish a theoretical basis for the development of innovative cardioprotective interventions.