At OS, dysregulation of many signaling pathways occurs in the bone microenvironment, including fibroblast growth factor (FGF), transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF1), bone morphogenetic proteins (BMPs), VEGF, hypoxia-induced factor (HIF1), a family of Wingless-type (WNT), Hedgehog (Hh), NOTCH MMTV integration sites involved in modulating self-renewal, differentiation, growth, drug resistance, and/or metastatic activity of OS and cancer stem cells (CSCs) [31,32]. The gene discussed is TGFB1; the disease is cancer.