Niches in cancer: from primary tumors to metastatic disease

Abstract Cancer progression does not occur in isolation: malignant-cell states and fates are shaped by specialized microenvironments, or cancer niches. Within primary tumors, vascular, stromal, immune and neural interactions create local hypoxic, metabolic and mechanical conditions that together influence malignant-cell behavior. These local environments sustain stem-like states, regulate immune surveillance and vascular remodeling, and influence dissemination and treatment response. Tumor-derived extracellular vesicles and other systemic signals connect primary tumors to distant organs, conditioning tissues before tumor-cell arrival and subsequently modulating disseminated tumor-cell seeding, dormancy, reactivation and outgrowth. Cancer niches therefore operate across spatial scales and disease stages, shaping tumor behavior in ways that cannot be explained by tumor-cell-intrinsic properties alone. Advances in single-cell and spatial profiling, organoid systems and intravital imaging are revealing their cellular composition, local architecture and evolution. In this review, we integrate primary, pre-metastatic and metastatic niche biology, examine how local environments evolve and influence one another during cancer progression, compare organ-specific metastatic niches and assess emerging therapeutic strategies. Effective niche-directed therapy will require identifying the interactions that sustain disease, showing that treatment disrupts them and determining which patients are most likely to benefit. Greater spatial, temporal and functional resolution may reveal new therapeutic vulnerabilities and create opportunities to prevent relapse and achieve more durable disease control.