Within this “ecological-evolutionary” framework, the study investigates the role of cytoplasmic HMGB1 in enhancing autophagy and promoting radioresistance in CRC through direct interaction with BECN1 and transcriptional regulation of ZNF460, identifying the HMGB1/ZNF460/BECN1 axis as a potentially actionable molecular target. This evidence concerns the gene BECN1 and colorectal carcinoma.