The effects of doxorubicin on cardiac calcium homeostasis and contractile function

Cancer is one of the leading causes of death globally and the number of cancer deaths is rising as a result of increased longevity. Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs used to treat various forms of cancer. However, its therapeutic utility is limited by its associated cardiotoxicity, specifically cardiac contractile dysfunction. Current evidence indicates that interference with cardiac intracellular calcium (Ca²⁺) homeostasis is one of the major causes among the molecular and cellular determinants of DOX-induced cardiotoxicity. This contributes to the development of cardiac contractile dysfunction, which remains a major concern and obstacle in clinical applications. This review comprehensively summarizes the effects of DOX on cardiac Ca²⁺ homeostasis and contractile function from in vitro, ex vivo, and in vivo studies. It also highlights the information essential for the potential interventions which may support the therapeutic effectiveness in clinical practice for the attenuation of cardiotoxicity in DOX-treated patients.