Role of the bone microenvironment in bone metastasis of malignant tumors - therapeutic implications

Bone is one of the most common sites for solid tumor metastasis. Bone metastasis of a malignant tumor seriously affects the quality of life and the overall survival of patients. Evidence has suggested that bone provides a favorable microenvironment that enables disseminated tumor cells to home, proliferate and colonize, leading to the formation of metastases. In the process of bone metastasis the bone microenvironment may be considered as an orchestra that plays a dissonant melody through blending (e.g. cross-talk between osteoclasts, osteoblasts and/or other cells), adding (e.g. a variety of biological factors) or taking away (e.g. blocking a specific pathway) players.

Here, we review the normal bone microenvironment, bone microenvironment-related factors that promote bone metastasis, as well as mechanisms underlying bone metastasis. In addition, we elude on directions for clinical bone metastasis management, focusing on potential therapeutic approaches to target bone microenvironment-related factors, including bisphosphonate, denosumab, CXCR4/CXCL12 antagonists and cathepsin K inhibitors.