While HMGB1-mediated autophagy typically serves as a protective mechanism against apoptosis in cancer cells [45], our study reveals a contrasting effect in the myocardium, where HMGB1 activates pathways such as HMGB1/TLR4/NFκB and HMGB1/extracellular signal-regulated kinase/ETS1, ultimately leading to apoptosis [46,47]. Here, TLR4 is linked to cancer.