Bone Metastasis: Molecular Mechanisms, Clinical Management, and Therapeutic Targets.

Bone metastasis (BoMet) is a common complication in various cancers. Approximately 20-30% of patients with cancer develop BoMet, which is most frequently associated with solid tumors, such as breast, prostate, and lung cancers. BoMet can lead to skeletal-related events such as fractures, bone pain, and hypercalcemia, negatively affecting the patient's quality of life and markedly shortening overall survival. The development of BoMet is a complex, multistep process driven by dynamic interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a supportive niche for disseminated tumor cells, where intricate signaling networks and stromal interactions regulate the initiation, dormancy, reactivation, and progression of BoMet. Although current bone-targeted therapies can reduce the incidence of these complications, the clinical outcomes for patients with BoMet remain poor. Therefore, elucidating the molecular mechanisms governing these interactions is essential for identifying new therapeutic strategies. This review systematically explores the molecular drivers of BoMet progression, dynamic interactions within the metastatic niche, available preclinical models, established treatment modalities, and emerging therapeutic approaches. As fundamental research continues to advance toward clinical translation, the outlook for patients with BoMet is expected to improve significantly.