HMGB1 and neoplasm: However, the translation of HMGB1-targeted therapy into clinical practice still faces three key challenges: (1) functional complexity: HMGB1 exhibits dual functions of promoting tumorigenesis and regulating antitumor immunity, and its effects are temporally and spatially regulated; (2) technical bottlenecks: RNA therapies inherently suffer from poor stability and low delivery efficiency; (3) tumor heterogeneity: the high genomic instability of OS limits the efficacy of single-target strategies.