In this context, it has been reported that bone-derived IGFs, which are released from bone in substantial amounts by osteoclastic bone resorption, activate IGF-IR/AKT/NF-kB signaling pathways in breast cancer cells that are colonizing the bone, thereby increasing their proliferation, decreasing apoptosis and thus promoting the development and progression of bone metastases [135,136]. The gene discussed is IGF1R; the disease is breast carcinoma.