Despite recent advances in prevention, screening, molecular characterization, and treatment, cancer evolution is still associated with late local, regional, or metastastic recurrence, even in early stages. Residual tumor cells can persist locally as cancer stem cells, in the blood flow as circulating tumor cells, and in distant organs as disseminated tumor cells or micrometastasis, defining three faces of minimal residual disease. Definition, preclinical models and clinical implications of these patterns will be detailed, with emphasis on overlaps and therapeutic implications, to determine whether minimal residual disease is only an old concept currently revisited, or a major shift in cancer paradigm.
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