Bone metastasis in cancer: from microenvironmental remodeling to precision therapy.

Abstract

Bone metastasis remains a major determinant of disability, treatment failure, and poor survival in solid tumors. It is no longer adequately explained as a late consequence of tumor spread or as a process driven only by osteoclast-mediated bone destruction. Current evidence supports a broader view in which bone metastasis emerges through progressive remodeling of a receptive niche, followed by selective tumor cell seeding, adaptive persistence, and eventual outgrowth under continued pressure from both local and systemic cues. In this framework, bone is not merely a target organ but an active biological system in which remodeling, hematopoiesis, immunity, and stromal signaling jointly shape metastatic fate. This perspective also helps explain why conventional management, although effective in reducing skeletal complications and relieving symptoms, rarely changes the long-term course of disease. In this review, we discuss how recent advances have redefined the biology of bone metastasis, from early niche conditioning to overt lesion progression, and examine how these insights are reshaping diagnosis and therapy. We further highlight the translational shift from lesion detection and antiresorptive treatment toward risk prediction, biological stratification, and mechanism-guided combination strategies. A more integrated understanding of tumor evolution within bone may provide the basis for earlier intervention and more durable disease control.