The role of long non-coding RNAs in therapy resistance of cervical cancer and therapeutic potential

Despite significant advances in preventive and early-detection strategies, cervical cancer (CC) continues to pose a substantial clinical burden, especially when confronting the challenge of therapy-resistant or recurrent disease. Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the development and progression of CC, particularly in mediating resistance to conventional and emerging therapies, including chemotherapy, radiotherapy, and immunotherapy. This review summarizes how specific lncRNAs drive therapeutic resistance through diverse mechanisms such as acting as competitive endogenous RNAs (ceRNAs) to sponge tumor-suppressive microRNAs, and by modulating key signaling pathways like PI3K/Akt and Wnt/β-catenin. Furthermore, we discuss the significant potential of lncRNAs as non-invasive diagnostic and prognostic biomarkers, detectable in liquid biopsies from patient serum or plasma, and as novel therapeutic targets. Advances in targeted strategies have primarily focused on the implementation of precise degradation or interference through antisense oligonucleotides (ASOs) and CRISPR-based systems, highlighting the translational potential of lncRNAs in overcoming refractory therapeutic resistance. Collectively, this review aims to provide a comprehensive overview of the multifaceted roles of lncRNAs in CC therapeutic resistance, offering critical insights that may accelerate the translation of lncRNA-based strategies into clinically actionable interventions to improve patient outcomes in therapy-resistant CC.