Weiyan Shan, Jingxia Zhang, Huan Shi, Jie Yu, Qiaoping Xu, Hongkai Shang
Ovarian cancer ranks as the third most common gynecological malignancy, yet it has the highest mortality and recurrence rates among all gynecologic cancers. Chemotherapy combined with immunomodulators and targeted agents, including PTX, ADR, PARPi, and platinum-based chemotherapeutics, markedly prolongs progression-free survival of patients with advanced ovarian cancer. Nevertheless, most advanced patients develop acquired drug resistance after long-term chemotherapy, resulting in poor clinical therapeutic efficacy. At present, the detailed mechanisms underlying ovarian cancer chemoresistance have been increasingly elucidated, including enhanced drug efflux, epigenetic modifications, DNA damage repair, apoptosis resistance, and EMT, among others. All the above biological processes are precisely modulated by upstream regulatory molecules, among which ncRNAs, covering miRNAs, lncRNAs and circRNAs, serve as core upstream regulators and exert pivotal functions in tumor malignant progression and chemotherapy resistance. Mechanistically, ncRNAs modulate the resistance via constructing diverse ceRNA competitive regulatory axes and governing canonical drug efflux, cancer stem cell and apoptotic signaling pathways in ovarian cancer. This review systematically summarizes the regulatory roles and molecular networks of ncRNAs in ovarian cancer chemoresistance. Notably, we further highlight the clinical translational potential of ncRNAs: ncRNAs can be applied for patient survival stratification, and act as druggable anti-tumor therapeutic targets to reverse chemoresistance, which provides novel clinical strategies for individualized treatment and curative effect improvement of refractory ovarian cancer.