HMGB1 and cancer: Considering the pertinence of RAGE in creating a cancer-endorsing niche by up regulating hypoxia and inflammation, and instigating the progression of cancer stem cells, via its various ligands, including AGEs, HMGB1 and S100 proteins in TME, the implications of RAGE targeted therapeutic intervention for effective cancer control cannot be underestimated (Table 3) [89, 136, 137].