AGER and neoplasm: Biological responses downstream of HMGB1 are implicated in promoting tumor proliferation, migration, and invasion by stimulating production of pro-inflammatory cytokines through RAGE-dependent pathways [37]; however, HMGB1 can signal through TLRs (TLR2 and TLR4), as well as RAGE, thereby triggering NF-kB, STAT-3, and MyD88-dependent pathways and promoting inflammation and tumorigenesis [126–128].