Cancer Cell Dormancy in Metastasis

Recurrent metastasis following extended periods of disease-free survival remains a common cause of morbidity and mortality for many cancer patients. Recurrence is thought to be mediated by tumor cells that escaped the primary site early in the disease course and colonize distant organs. In these locations, cells adapt to the local environment, entering a state of longterm dormancy in which they can resist therapy. Then, through mechanisms that are poorly understood, a proportion of these cells are reactivated and become proliferative, forming lethal metastases. Here, we discuss disseminated tumor cell dormancy in recurrent metastasis. We discuss mechanisms known to control entrance of cells into dormancy, highlighting the relevant microenvironments or niches in which these cells reside and mechanisms known to be involved in dormant cell reactivation. Finally, we consider emerging therapeutic approaches aimed at eradicating residual disease and preventing metastatic relapse.