Ovarian cancer patients with platinum resistance face a dismal five-year survival rate of only 30%, owing to the limited efficacy of current therapeutic options. Existing research often focuses on individual epigenetic modifications, which hampers a systematic understanding of resistance mechanisms and their clinical translation. To address this, our review integrates current evidence to propose an “Epigenetic Resistance Stability Network” model, which comprises three core components: (i) four foundational layers, each with distinct roles in cisplatin resistance. These include DNA methylation (e.g., SFRP5 hypermethylation activating the Wnt pathway), non-coding RNAs (ncRNAs), RNA modifications, and histone modifications, which govern gene expression, post-transcriptional regulation, RNA function, and chromatin architecture, respectively. (ii) three interactive networks: “DNA methylation/miRNA feedback loops,” “lncRNA/histone modification cascades,” and “circRNA/m6A synergistic stabilization.” These networks sustain the resistant phenotype by interlinking key nodes across the four foundational layers. (iii) a theoretical framework encompassing two parts: the “Epigenetic Compensation Network” theory (explaining how tumors evade single-target therapies) and the “Epigenetic Temporal Regulation” model (outlining resistance progression: “miRNA response → methylation consolidation → chromatin stabilization”). Building on this model, we outline a translational roadmap involving “biomarker validation (e.g., SFRP5 methylation, circITGB6),” “combination therapy development,” and “personalized intervention,” offering novel insights for overcoming cisplatin resistance and improving patient outcomes in ovarian cancer.
Tang et al. (Fri,) studied this question.