Intriguingly, tumor-derived S100A9—released as a DAMP—likely interacts with RAGE and TLR4 on both cancer and stromal cells, triggering NF-κB and MAPK/ERK signaling cascades that promote a pro-inflammatory microenvironment, enhance tumor cell proliferation and facilitate pre-metastatic niche formation. This evidence concerns the gene S100A9 and neoplasm.