Targeting RANKL in breast cancer: bone metastasis and beyond

In breast cancer, RANK ligand (RANKL) appears to play an important role in the process of chemotaxis between circulating tumor cells and the bone microenvironment, which enables RANK-expressing breast cancer cells to migrate into the bone. Mounting clinical evidence has further demonstrated that the anti-RANKL monoclonal antibody; denosumab is the most effective approach in the prevention of skeletal-related events. On the other hand, inhibiting RANKL in preclinical models, not only reduced breast cancer formation but also decreased the development of lung metastases, suggesting RANKL as a novel target for breast cancer chemoprevention. In addition, recent data have pointed to a potential role of RANKL in the biology of breast cancer arising at a young age. Hence, RANKL emerges as a key molecule, not only in the field of breast cancer bone metastasis but also in the biology of breast cancer as a whole.