Molecular Landscapes of Tumor Dormancy in Gynecologic Malignancies: From Survival Mechanisms to Precision Interception

Late recurrence in gynecologic malignancies is associated with tumor dormancy and persistent minimal residual disease (MRD). Although current treatments reduce proliferating tumor burden, residual cells may survive therapy and drive delayed relapse. This Review examines dormancy in ovarian, endometrial, and cervical cancers using entry, maintenance, and awakening as an organizing framework rather than a universally demonstrated sequence. Direct evidence is concentrated in ovarian cancer, whereas evidence in endometrial and cervical cancers remains predominantly indirect. We delineate candidate biological dependencies-including redox control, lipid peroxidation buffering, mitochondrial plasticity, adaptive stress-response programs, epigenetic and post-transcriptional plasticity, immune regulation, and extracellular matrix remodeling-rather than established vulnerabilities. On this basis, we evaluate two biologically distinct investigational concepts: suppression of reactivation-associated signals to prolong clinical latency, and state modulation followed by biomarker-defined treatment, discussed within established disease-specific care pathways. Finally, we propose a translational framework combining longitudinal liquid biopsy with spatial and single-cell profiling for MRD monitoring, biological stratification, and future probabilistic inference of residual-cell states. Together, these concepts support a shift from reactive relapse treatment toward evidence- and risk-constrained recurrence-interception research and provide a framework for validating residual-state biomarkers and therapeutic dependencies in gynecologic malignancies.