HMGB1 and neoplasm: However, in the case ofnormal (non-immunogenic) apoptosis, HMGB1 is not released from the tightlypacked apoptotic cell nuclei [54].According to Luo et al. [54], therelease of HMGB1 from necrotic tumor cells treated with doxorubicin, whichcauses necrosis when used at high concentrations [55], contributes to the resumption of tumor growth andmetastasis development via the RAGE system activation pathway.