抗肿瘤靶点鉴定是成功研发高效低毒分子靶向药物的基础。申请人在此方向取得的成绩包括：(1) 系统发现Neddylation修饰及其底物CRL泛素连接酶超家族在肿瘤内异常活化；(2) 深入阐明靶向Neddylation-CRL通路抗肿瘤治疗的关键作用机制；(3) 成功鉴定ROC1和ROC2（CRL核心亚基）为新的抗肿瘤分子靶点，相关发现有力促进了针对Neddylation-CRL通路靶向新药的研发进程。在J Natl Cancer Inst、J Clin Invest、Autophagy、Cancer Res、Clin Cancer Res、Cell Death Differ、Mol Cell Proteomics、Cell Death Disease和J Biol Chem等期刊发表36篇论文。基于前期良好基础，申请人拟深入阐明Neddylation修饰在肿瘤内活化的调控机制及其促癌机理。

Identification and validation of anticancer targets are prerequisites and foundations for the development of molecular targeted drugs with high efficiency and low toxicity for cancer therapy. The applicant has made a series of original academic achievements in this field, including: 1) the discovery of the overactivation of Neddylation pathway and its classical substrates CRL ubiquitin ligases in human cancers; 2) the deep elucidation of several key mechanisms of anticancer effects of Neddylation-CRL inhibition; 3) the successful identification of ROC1 and ROC2, two core components of CRL ubiquitin ligases, as new anticancer targets. These findings strongly promote drug discovery targeting Neddylation-CRL axis. So far, the applicant has published 36 articles in academic journals, including J Natl Cancer Inst（JNCI）、J Clin Invest（JCI）、Autophagy、Cancer Res、Clin Cancer Res、Cell Death Differ、Mol Cell Proteomics、Cell Death Disease and J Biol Chem, etc. In this project, the applicant will further explore the upstream modulation mechanisms of Neddylation overactivation and the downstream mechanisms of overactivated Neddylation in the promotion of lung carcinogenesis and cancer progression.