While early models suggested CSCs originate from normal stem cells, such as haematopoietic stem cells (HSCs), evidence now indicates that CSCs can also arise from differentiated cancer cells undergoing dedifferentiation under the influence of the TME [52] The dynamic interactions between CSCs and their surrounding stromal cells, immune infiltrates, and extracellular matrix components are mediated by pathways such as NF-κB, Wnt/β-catenin, and Hedgehog [53–55]. The gene discussed is NFKB1; the disease is cancer.