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