The Interplay Between Autophagy and Senescence in Anthracycline Cardiotoxicity

Doxorubicin (DOXO) is a highly effective chemotherapeutic drug employed for the treatment of a wide spectrum of cancers, spanning from solid tumours to haematopoietic malignancies. However, its clinical use is hampered by severe and dose-dependent cardiac side effects that ultimately lead to heart failure (HF).

Mitochondrial dysfunction and oxidative stress are well-established mechanisms of DOXO-induced cardiotoxicity, although recent evidence suggests that deregulation of other biological processes, like autophagy, could be involved. It is increasingly recognized that autophagy deregulation is intimately interconnected with the initiation of detrimental cellular responses, including autosis and senescence, raising the possibility of using autophagy modulators as well as senolytics and senomorphics for preventing DOXO cardiotoxicity. This review aims at providing an overview of the signalling pathways that are common to autophagy and senescence, with a special focus on how the relationship between these two processes is deregulated in response to cardiotoxic treatments. Finally, we will discuss the potential therapeutic utility of drugs modulating autophagy and/or senescence for counteracting DOXO cardiotoxicity.