Bone is one of the most frequent loci of cancer metastases. Recent advances in treatment have improved the prognosis of metastatic cancer, including bone metastasis, highlighting the importance of treating bone metastasis to reduce incidence of skeletal complications and improve patients' QOL. It has become evident that bone microenvironment such as interaction of cancer cells and osteoclasts or osteoblasts is important for establishment and progression of bone metastases. Bone-targeted therapy that modulates osteoclasts or osteoblasts has been developed recently.
Bisphosphonates (BPs), especially zoledronic acid, decrease skeletal-related events (SRE) and are commonly used for the treatment of bone metastasis. BPs also have shown evidences of anti-tumor efficacy in several clinical trials, such as ABCSG-12 and AZURE in breast cancer patients and MRC Myeloma IX in myeloma patients. However, the outcomes of BP therapy leave room for improvement with regards to their efficacy, safety, and convenience, and other bone-targeted therapies are also being developed.
Many studies have indicated that receptor-activator of NFkappaB ligand (RANKL) plays an important role in bone resorption by osteoclasts. Denosumab is a fully human monoclonal anti-RANKL antibody, which suppresses differentiation, activation and survival of osteoclasts by inhibiting the binding of RANKL to its receptor, RANK. In three phase III clinical trials, denosumab decreased the time-to-first and time-to-first-and-subsequent SRE compared with zoledronic acid in advanced cancer patients with bone metastases, and denosumab was recently approved for bone lesions of solid cancer and myeloma. Other targeted agents such as SRC inhibitors and c-MET inhibitors are also being developed. Bone metastasis treatment for cancer patients is expected to evolve further with the development of new bone-targeted agents in the near future.