HMGB1 was initially identified as a nuclear DNA-binding protein. As such, it plays a role in the transcription of several genes, some of which include those that have been implicated in cancer development including E-selectin, TNFα, insulin receptor, and BRCA (93) (94) (95) (96) . Furthermore, cancer cells that have undergone necrotic cell death can release HMGB1 into the local microenvironment. Extracellular HMGB1 can lead to chronic inflammatory/reparative responses that, in the setting of cancer, may lead to tumor cell survival, expansion, and metastases (97) . Interestingly, numerous studies suggest that HMGB-1 plays a role in metastasis development, and thus links it to poor prognosis in a variety of cancers including prostate, breast, pancreas, and colon (98) (99) (100) (101) (102) (103) (104) (105) (106) .