By contrast, fully oxidized HMGB1 loses affinity for RAGE and Beclin1 and instead enhances drug cytotoxicity by promoting apoptosis through the caspase-9/-3 intrinsic pathway [96,97], positioning HMGB1 as a molecular switch that regulates autophagy and apoptosis within the tumor microenvironment. This evidence concerns the gene BECN1 and neoplasm.