<p>Lung cancer remains a major global health challenge, with non-small cell lung cancer (NSCLC) accounting for nearly 85% of cases and deaths. Although advances in targeted therapy and immunotherapy have improved patient outcomes, drug resistance and limited long-term survival continue to pose serious obstacles. Ferroptosis, an iron-dependent and lipid peroxidation–driven form of regulated cell death, has attracted growing attention as a novel therapeutic approach to address these challenges. At the same time, non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, are increasingly recognized as crucial regulators of cancer progression, therapy resistance, and cellular homeostasis. Recent studies reveal that ncRNAs and ferroptosis are closely interconnected in lung cancer, with ncRNAs influencing iron metabolism, antioxidant defense, and lipid peroxidation, thereby modulating sensitivity or resistance to ferroptotic death. Importantly, this crosstalk not only shapes tumor biology but also provides opportunities for clinical translation. Ferroptosis-related ncRNAs are emerging as potential biomarkers for prognosis, therapeutic response, and disease stratification. In addition, pharmacological induction of ferroptosis, combined with modulation of specific ncRNAs, offers a promising strategy to overcome resistance to chemotherapy, radiotherapy, and immunotherapy. This review highlights the latest advances in understanding the interplay between ncRNAs and ferroptosis in lung cancer and discusses their implications for precision medicine. By integrating ferroptosis induction with ncRNA-targeted strategies, new avenues may emerge for developing more effective and personalized therapies against NSCLC.</p>

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The intersection of ferroptosis and non-coding RNAs: a novel approach to lung cancer

  • Jian Ding

摘要

Lung cancer remains a major global health challenge, with non-small cell lung cancer (NSCLC) accounting for nearly 85% of cases and deaths. Although advances in targeted therapy and immunotherapy have improved patient outcomes, drug resistance and limited long-term survival continue to pose serious obstacles. Ferroptosis, an iron-dependent and lipid peroxidation–driven form of regulated cell death, has attracted growing attention as a novel therapeutic approach to address these challenges. At the same time, non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, are increasingly recognized as crucial regulators of cancer progression, therapy resistance, and cellular homeostasis. Recent studies reveal that ncRNAs and ferroptosis are closely interconnected in lung cancer, with ncRNAs influencing iron metabolism, antioxidant defense, and lipid peroxidation, thereby modulating sensitivity or resistance to ferroptotic death. Importantly, this crosstalk not only shapes tumor biology but also provides opportunities for clinical translation. Ferroptosis-related ncRNAs are emerging as potential biomarkers for prognosis, therapeutic response, and disease stratification. In addition, pharmacological induction of ferroptosis, combined with modulation of specific ncRNAs, offers a promising strategy to overcome resistance to chemotherapy, radiotherapy, and immunotherapy. This review highlights the latest advances in understanding the interplay between ncRNAs and ferroptosis in lung cancer and discusses their implications for precision medicine. By integrating ferroptosis induction with ncRNA-targeted strategies, new avenues may emerge for developing more effective and personalized therapies against NSCLC.