RANK as a Therapeutic Target in Cancer

The RANK signaling pathway was identified as a significant target in breast cancer due to its role in mediating the pro-tumorigenic effects of progesterone in the mammary gland. RANKL inhibitors, already used by thousands of cancer patients for bone metastasis management, highlighted the pathway's importance in osteoclastogenesis and bone resorption. Additionally, RANK signaling influenced immunity and inflammation, being crucial for lymph node organogenesis, thymic development, self-tolerance, and immune cell activation. It also affected mammary epithelial differentiation, hair follicle, and epidermal stem cell homeostasis, marking RANK as a key regulator of epithelial stemness. The document reviewed RANK's functions in bone remodeling, immune response, and epithelial differentiation, and discussed its diverse effects on cancer, including bone metastasis and immune and cancer-cell interactions.