Mimicking mammalian hibernation to lock cancer cells in safe quiescence

Relapse in cancer is often driven by disseminated tumor cells (DTCs) that enter a dormant, non-proliferative state and later reactivate. Conventional pharmacology primarily focuses on eradicating dividing cells but lacks tools to induce and maintain a benign dormant state. Mammalian hibernation offers a natural, reversible model of systemic cellular quiescence mediated by dynamic epigenetic reprogramming. Here, we propose that studying and pharmacologically mimicking the epigenetic landscape of hibernators may provide a novel class of agents, “dormostatics”, to lock DTCs into safe dormancy. We discuss key epigenetic features of torpor (DNA methylation shifts, histone modifications, sirtuin and SUMO pathways), their analogues in cancer cell biology, and articulate a translational roadmap toward epigenetic dormancy pharmacology. Finally, we highlight major outstanding questions and key clinical considerations.