Cell biology of cancer dormancy

Cancer dormancy is a dynamic state in which residual disseminated tumor cells persist without overt expansion yet retain the capacity to reawaken and drive metastatic relapses. In this Review, we discuss major conceptual and mechanistic advances in the cell biology of cancer dormancy. Firstly, we summarize the recognized principal forms and constraints of dormancy, including cellular and tumor mass dormancy, metabolic and extracellular matrix-dependent growth restriction, immune-mediated equilibrium, angiogenic limitation and drug-tolerant persistence states. Next, we examine organ-specific dormancy switches in major clinical sites of metastasis (bone, liver, lung and brain), focusing on how local stromal, vascular, epithelial, immune and neural cues govern the balance between long-term dormancy or quiescence and metastatic outgrowth. Finally, we review the evolution of dormancy-focused therapeutic strategies, from the early attempts to eliminate minimal residual disease to newer approaches targeting dormant-cell survival pathways and the metastatic niche. We conclude by discussing the major unresolved questions in this field, including dormant-state heterogeneity, organ-specific regulation of dormancy and the timing of reactivation, all of which will be central to designing future strategies that prevent metastatic recurrence.