Early origin of cancer metastases: dissemination and evolution of premalignant cells

Metastasis is the main cause of death by cancer. Hence, establishing predictive markers constitutes a major clinical objective. The capacity for a tumor cell to migrate and survive from a primary tumor is often described as the ultimate step of Darwinian selection. These metastatic cells are believed to emerge from a subpopulation of cells present in a primary tumor. In line with this hypothesis, various gene "signatures" associated with poor prognosis and/or with tumors displaying high metastatic potential have been promoted. However, over the last few years, a growing body of evidence supports the idea that metastatic cells disseminate early from the primordial tumor and evolve independently of it. Herein, we propose to review to the data favoring this alternative model and discuss the interplay between metastatic mechanisms and failsafe mechanism pathways.