Targeting autophagy in doxorubicin-induced cardiotoxicity: A comprehensive review of scientific landscapes and therapeutic innovations

Abstract

Doxorubicin (DOX)-induced cardiotoxicity (DIC) poses a major threat to elderly cancer patients, often leading to severe cardiac dysfunction and complicating the outcome of cancer treatment. Autophagy is one of the core mechanisms of DIC and is considered a key therapeutic target. We analyzed the status of research in the field of autophagy in DIC via bibliometric methods. A total of 292 publications related to this topic were identified and included. Furthermore, based on included publications and relevant studies in the field of geriatrics, the characteristics of autophagy in the aging heart and DIC, therapeutic strategies targeting autophagy, and challenges in clinical translation were summarized. Our review reveals that research hotspots in the field focus on how to balance the relationship between the effects of cancer treatment and cardiotoxicity, and the frontiers focus on exploring new therapeutic strategies via autophagy regulation. The autophagy ability of aging hearts is significantly reduced, which accelerates the occurrence of myocardial fibrosis, systolic dysfunction, and chronic inflammation. Autophagy has significant bidirectional regulatory effects on DIC. Additionally, the dynamic regulation of autophagy is significantly affected by dose gradients of DOX, exposure time windows, experimental models, and differences in administration methods. Drugs such as dexrazoxane and melatonin, as well as rehabilitation therapies such as aerobic training and resistance training, can regulate cardiomyocyte autophagy and have clinical translational potential. However, age heterogeneity in existing clinical studies undermines the generalizability of findings to elderly cancer patients. Future therapeutic optimization requires regimen customization based on elderly specific organ function decline patterns.