Year: 2026
Type: review
Abstract: High-grade serous ovarian carcinoma (HGSOC) recurs in most patients despite initial responses to chemotherapy and poly(ADP-ribose) polymerase inhibition. A leading explanation for the high rates of recurrence is the presence of minimal residual disease (MRD) comprised of drug-tolerant persister (DTP) cells that survive therapy through reversible epigenetic reprogramming. DTPs have various adaptations that enable them to tolerate therapy and eventually develop into resistant clones, including quiescence, metabolic and hypoxic stress responses, epithelial-mesenchymal plasticity, and immune evasion. Here, we discuss evidence from ovarian cancer of epigenetic mechanisms that coordinate DTP phenotypes, including DNA methylation, histone post-translational modifications, enhancer rewiring, and transcription factor gene-regulatory networks. Based on therapeutic vulnerabilities identified from increased resolution of DTPs, we highlight epigenetic therapies that are currently in clinical trials aimed at depleting MRD to delay or prevent relapse in HGSOC. Finally, we outline emerging technologies that have the potential to detect and monitor persister states in patients, including single-cell transcriptomic and epigenomic profiling, long-read sequencing, and spatial mapping of tumor biopsies.
Source: NAR Cancer
Institution: Mayo Clinic
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,583
Awards: G1172505002, DECIPHERING THE ROLE OF CANCER STEM CELLS IN CHEMOTHERAPY RESISTANCE IN HIGH GRADE SEROUS CARCINOMA, DECIPHERING THE REGULATION OF IMMUNE CHECKPOINTS IN HIGH-GRADE SEROUS OVARIAN CANCER STEM CELLS, G4809475267, Paul Calabresi Program in Clinical/Translational Research at Mayo Clinic, MSTP at Mayo Clinic Rochester, Mayo Clinic Ovarian Cancer SPORE
OpenAlex ID: W7223176171