Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer

Lung cancer is the most common but fatal malignant tumor worldwide. Patients with lung cancer experienced a relatively low 5-year overall survival rate, and issues such as metastasis and drug resistance remain prominent challenges in its clinical management. Neddylation, a novel type of post-translational modification, was overactivated in lung cancer and was closely associated with its occurrence, development, metastasis, and drug resistance. This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation, metastasis, and drug resistance mechanisms, with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family. Meanwhile, it concludes the current advances in potential therapeutic agents targeting neddylation-related targets, including small-molecule compounds (such as Pevonedistat) and natural extracts (such as arctigenin). Finally, the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment. In conclusion, we aim to systematically summarize the biological process of neddylation, critically explore its roles in lung cancer proliferation, metastasis, and drug resistance, and evaluate the therapeutic potential of neddylation-targeting agents.