A CTC/DTC-centered temporal framework of bone metastasis: From dissemination to dormancy and reactivation.

Bone metastasis is a major cause of morbidity and poor survival in solid tumors, yet its progression is often recognized only after overt lesion formation. In this review, we propose a circulating tumor cell/disseminated tumor cell (CTC/DTC)-centered temporal framework that conceptualizes bone metastasis as a sequential and selection-driven process linking dissemination, bone-specific homing, DTC establishment, dormancy, and reactivation. We summarize the key cellular and molecular mechanisms governing these transitions, with particular emphasis on tumor cell plasticity, bone marrow niche interactions, and the dormancy-reactivation interface. We further discuss the translational relevance of this approach for risk stratification, minimal residual disease assessment, treatment monitoring, and emerging experimental strategies, including single-cell multi-omics, spatial omics and biomimetic bone microenvironment models. This perspective shifts the view of bone metastasis from a static, imaging-detectable lesion to a time-resolved biological process and highlights potential windows for earlier risk assessment, disease monitoring, and biology-guided intervention.