The above signaling cascade can be activated by various factors situated in the TME, with the most common among them being growth factors secreted by cancer cells, pro-inflammatory cytokines, calcium binding proteins (calgranulin A/B; S100A8/A9), heat shock protein (HSP72), high-mobility group box 1 (HMGB1), and other molecules in the TME [15,24,25]. This evidence concerns the gene HMGB1 and cancer.