Recently, we described how geminin helps acetylate chromatic HMGB1 and release it from GemOE tumor cells10, where it through binding to receptor for advanced glycation end products (RAGE) on GemOE tumor cells activates NF-κB-induced survival, especially those exposed to the harsh condition of hypoxia and inflammation10 within the tumor core (aka “aggressiveness niche”20). Here, HMGB1 is linked to neoplasm.