Cuproptosis and lncRNAs: Interplay in cancer immunity, prognosis, and chemotherapy sensitivity

Cuproptosis, a copper-dependent regulated cell death pathway, and long non-coding RNAs (lncRNAs) are pivotal emerging regulators in cancer biology. This review proposes an integrative"cuproptosis-lncRNA axis" as a central network governing tumor immunity, prognosis, and therapy sensitivity. We introduce a functional taxonomy, classifying cuproptosis-related lncRNAs into three functional archetypes:ceRNA sponges, epigenetic regulators, and signaling hubs. We elucidate how each category fine-tunes copper homeostasis, mitochondrial proteotoxic stress, and downstream malignant phenotypes. This axis uniquely bridges mitochondrial metabolism, cell death execution, and immune modulation, offering a novel conceptual framework for understanding cancer progression. We further discuss how targeting this axis-through strategies tailored to lncRNA functional class-can overcome immune evasion and chemoresistance, providing a roadmap for precision oncology. The emerging concept of "copper immunometabolism" within the tumor microenvironment is also highlighted. The integration of cuproptosis-directed therapies with lncRNA targeting holds significant promise for developing more effective, personalized cancer treatments.