Stress hormones and immune cells called neutrophils may contribute to the recurrence of tumors years after treatment by awakening dormant cancer cells, suggests a study of mice and data from 80 patients with lung cancer. The experiments help answer the enduring question of why cancers can return long after seemingly being cured with chemotherapy or surgery; the results also hint that targeting stress hormones with approved drugs known as beta-blockers could potentially help prevent tumors from returning. The recurrence of tumors is one of the biggest causes of deaths in cancer patients, but it's unclear exactly what biological mechanisms prompt tumors to recur. However, studies have suggested that recurrence unfolds as dormant tumor cells, which initially spread during the early stages of cancer, become active once more. Michela Perego and colleagues discovered that stress hormones such as norepinephrine reactivated dormant lung and ovarian cancer cells in mice. Specifically, the scientists found that exposing the mice to stressful situations elevated levels of stress hormones, which caused neutrophils to release S100A8/A9 proteins and fatty molecules that in turn prompted tumor cells to reawaken from dormancy. However, tumor cells remained dormant in stressed-out mice that received an experimental beta-blocker. The team also studied serum samples from 80 patients who had their lung cancers surgically removed and saw that patients who harbored higher concentrations of S100A8/A9 were more likely to have experienced recurrence 33 months after surgery. Perego et al. say that beta blockers or compounds that target S100A8/A9 proteins should be evaluated as potential therapies to disrupt the reactivation process, but stress the need for more sophisticated models of tumor cell dormancy.