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REVIEW

Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer

Jiayu Zou1,2,3, Yajie Lu3, Jiaqi Li3, Zhaokai Zhou4,5, Fu Peng3, Pu Qiu2,*, Hailin Tang6, Cheng Peng1,*
1 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
2 Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Guangzhou, 511436, China
3 Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
4 Department of Urology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
5 National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
6 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
* Corresponding Author: Pu Qiu. Email: email; Cheng Peng. Email: email

Oncology Research https://doi.org/10.32604/or.2025.071940

Received 16 August 2025; Accepted 21 November 2025; Published online 23 December 2025

Abstract

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.

Keywords

Neddylation; lung cancer; cancer growth; metastasis; drug resistance; drug candidates

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