IGF1 and cancer: These secretions activate the RANK/RANKL and Notch pathways, stimulating osteoclastogenesis and activation, exacerbating bone destruction, and providing a conducive environment for metastatic growth.154,210,211 Osteolysis in metastatic bone releases of key biological factors, including transforming growth factor beta (TGF-β), IGF-1, and calcium.200,212,213 These substances profoundly influence cancer cell growth, proliferation, and propensity for bone metastasis, thereby creating an environment conducive to the establishment and progression of skeletal lesions.