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
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（10）
• 所属期刊栏目: Original articles
• 页码范围: 3120-3133
• 页数: 14页
• 语种: 英文

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 therapy.So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy.In 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) cells.Mechanistically,PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-Ll expression in NSCLC cells and increased the CD3+ T cells infiltration and functions in tumor tissue.There was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with NSCLC.And the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage therapy.Our results demonstrate that PD0325901,an ERK inhibitor,can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo models.And 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.