Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies

Tumor dormancy represents a clinically significant but poorly understood state in which disseminated cancer cells persist in a quiescent, non-proliferative state, evading conventional therapies and driving late relapse. This review summarizes recent advancements in experimental models-both in vitro and in vivo-that recapitulate the full spectrum of dormancy, including its induction, maintenance, and reactivation. Crucial intrinsic pathways such as ERK/p38 signaling shifts, epigenetic remodeling, and metabolic adaptations and microenvironmental and immune-mediated cues that regulate dormant cell fate are discussed. Therapeutic strategies aimed at maintaining dormancy, reactivating dormant cells for elimination, or directly targeting their survival pathways have been highlighted. By integrating insights from model systems, molecular regulation, and therapy, this review aims to provide a comprehensive framework that informs future efforts to target dormant cancer cells and ultimately reduce recurrence and improve patient outcomes.