AGER and neoplasm: During cancer progression, HMGB1 has been observed to modulate the NF-κB, PI3K/AKT and mitogen-activated protein kinase (MAPK) signaling pathways by interacting with the receptor for advanced glycation end products (RAGE), while blockade of the HMGB1/RAGE interaction has been demonstrated to suppress tumor growth and metastasis (25,26).