The force awakens: metastatic dormant cancer cells.

Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they can interpret homoeostatic signals from the microenvironment, thereby evading immune surveillance and chemotherapy. Eventually, DCCs can reawaken in response to signals, which are not yet fully understood, resulting in recurrence and metastasis. Therefore, understanding the biology of DCC reawakening is key to preventing metastasis. Over the last decade, a growing body of literature has revealed the mechanisms involved in cancer dormancy and reawakening. The cytotoxic activity of immune cells can cause cancer cells to enter a dormant state, and chronic inflammation can reactivate cancer proliferation at distant sites. Upon the binding of circulating DCCs to extracellular molecules, various signaling cascades are activated and reinitiate cell proliferation. In the present review, we attempt to consolidate the existing literature to provide a framework for the understanding of this crucial step in cancer progression. Preventing dormant cancer cells (DCCs) from reawakening could be key to preventing cancer recurrence. During cancer progression, dormant tumor cells can travel through the bloodstream, reawakening to form tumors in distant tissues. These tumors, known as metastases, are difficult to treat. The signals that cue DCCs to enter and exit dormancy are poorly understood. In a review, Jeong-Seok Nam and So-Yeon Park at the Gwangju Institute of Science and Technology in South Korea report that DCCs often enter dormancy to evade attack by immune cells. Once in a new location, DCCs receive signals from the surrounding tissue, which can trigger tumor development. DCCs can also be reactivated by chronic inflammation. Signals that block reactivation of DCCs are currently being tested as potential therapeutics, and may help in the fight against this leading cause of death from cancer.