PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

作     者：Min Luo Yuhui Xia Fang Wang Hong Zhang Danting Su Chaoyue Su Chuan Yang Shaocong Wu Sainan An Suxia Lin Liwu Fu Min Luo;Yuhui Xia;Fang Wang;Hong Zhang;Danting Su;Chaoyue Su;Chuan Yang;Shaocong Wu;Sainan An;Suxia Lin;Liwu Fu

作者机构：State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-sen University Cancer CenterGuangzhou 510060China Pharmacy CollegeGuangzhou Medical UniversityGuangzhou 510182China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第10期

页      面：3120-3133页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：the grants from the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”,China(No:2018ZX09711002) the National Natural Science Foundation of China(No:81673463) 

主　　题：ERK1/2 PD-L1 PD-1 PD0325901 NSCLC Immunotherapy Targeted therapy Combination therapy 

摘      要：ERK pathway regulated the programmed death ligand-1(PD-L1)expression which was linked to the response of programmed death-1(PD-1)/PD-L1 blockade *** it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer *** this study,PD0325901,an oral potent ERK inhibitor,strongly enhanced the efficacy of PD-1 antibody in vitro and in vivo models in non-small cell lung carcinoma(NSCLC)***,PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-L1 expression in NSCLC cells and increased the CD3+T cells infiltration and functions in tumor *** was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with *** the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage *** results demonstrate that PD0325901,an ERK inhibitor,can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo *** the combination of ERK inhibitor such as PD0325901 and PD-1/PD-L1 blockage is a promising regimen and encouraged to be further confirmed in the treatment of patients with NSCLC.