How do you study something if you can’t be sure it’s there? And how do you know it’s there if you’re not quite sure what to look for?
Those are the core challenges facing researchers who study dormant cancer cells: rare, solitary cells that can survive initial therapy, slip away from the primary tumor, and persist—often invisibly—for years. Then, long after a patient is thought to be cancer-free, they can “wake up” and seed a recurrence that’s frequently more aggressive and harder to treat.
This review summarizes the current state of this intractable problem. What exactly are dormant cancer cells, and how can we reliably identify them in a sea of trillions of normal cells? How do they resemble—and differ from—the primary tumor? When and how do they escape, and what does it even mean, biologically, to be “dormant”? What triggers dormancy, what sustains it, and what flips the switch to reawakening? How did these cells withstand the original treatment, and how do they evade immune surveillance for so long? What are the therapeutic vulnerabilities of dormant cells, and what are their therapeutic vulnerabilities once these cells reawaken?
Progress has been slow, but the field is finally gaining traction. As new tools make dormant cells easier to define and detect, discoveries should accelerate—leading to therapies that can eliminate them before they ever reawaken.
