Therapy resistance-related ncRNAs in cervical cancer: biomarkers and therapeutic targets.

BACKGROUND: Cervical cancer remains a major cause of cancer-related morbidity and mortality, and resistance to chemoradiotherapy, systemic chemotherapy, and emerging targeted or immune-based therapies continues to limit durable disease control. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and extracellular-vesicle-associated transcripts, are increasingly recognized as regulators of DNA-damage repair, apoptosis, epithelial-mesenchymal plasticity, stemness, metabolic adaptation, ferroptosis, and tumor-microenvironmental communication in treated cervical tumors. OBJECTIVE: This narrative review aimed to critically synthesize therapy resistance-related ncRNAs in cervical cancer using a resistance-centered and translational framework that extends beyond previous reviews focused predominantly on individual ncRNA classes, cisplatin resistance, or broader ncRNA biology. The review integrates miRNAs, lncRNAs, circRNAs, and extracellular-vesicle-associated ncRNAs across therapeutic modalities and evaluates them according to recurrent resistance mechanisms, level of experimental or patient-associated validation, biomarker readiness, and therapeutic tractability. METHODS: A narrative literature search of PubMed, Scopus, Web of Science, and Google Scholar was conducted up to June 2026 to identify studies linking miRNAs, lncRNAs, circRNAs, and extracellular-vesicle-associated ncRNAs with treatment resistance, treatment sensitivity, or clinical response in cervical cancer. Evidence was synthesized according to treatment modality, mechanistic resistance program, biological source, level of validation, biomarker readiness, and therapeutic tractability. RESULTS: The available evidence indicates that ncRNA networks contribute to therapy resistance by regulating DNA-damage repair, survival signaling, epithelial-mesenchymal transition, cancer stem-cell phenotypes, drug efflux, metabolic adaptation, ferroptosis, and exosome-mediated intercellular communication. Conversely, several ncRNAs can restore chemosensitivity or radiosensitivity by promoting apoptosis or ferroptosis and impairing repair of therapy-induced damage. Particular attention is given to circulating and exosomal ncRNAs as investigational biomarker candidates that have shown associations with treatment response or clinical outcome, while emphasizing that prospective and independent clinical validation remains lacking. Finally, antisense oligonucleotides, small interfering RNAs, miRNA mimics, anti-miRs, nanoparticle systems, and engineered exosomes are discussed as experimental or early translational therapeutic approaches, with particular attention to unresolved challenges related to delivery, safety, target specificity, and context-dependent function. CONCLUSION: By moving beyond a transcript-by-transcript catalogue, this review identifies ncRNA networks and individual candidates that warrant further biomarker validation or preclinical therapeutic development rather than implying current clinical readiness.