Clinical implications of EGFR‐associated MAPK/ERK pathway in multiple primary lung cancer

In multiple primary lung cancers (MPLCs), surgery achieved a 5-year overall survival rate that varies from 27.4% to 95.8%.1 Targeted therapy has been applied to MPLC patients with different responses due to driver mutation heterogeneity.2 Meanwhile, two clinical trials are testing immune checkpoint...

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Published in:	Clinical and translational medicine 2022-05, Vol.12 (5), p.e847-n/a
Main Authors:	Liang, Naixin, Bing, Zhongxing, Wang, Yadong, Liu, Xinyu, Guo, Chao, Cao, Lei, Xu, Yuan, Song, Yang, Gao, Chao, Tian, Zhenhuan, Wu, Pancheng, Xue, Jianchao, Li, Bowen, Jia, Ziqi, Yang, Xiaoying, Wu, Yijun, Yu, Ruoying, Liu, Rui, Chen, Xiaoxi, Ou, Qiuxiang, Bao, Hua, Wu, Xue, Cao, Zhili, Li, Ji, Li, Shanqing
Format:	Article
Language:	eng
Subjects:	Cancer therapies Chemotherapy ErbB Receptors - genetics ErbB Receptors - metabolism Humans Immunotherapy Kinases Letter to the Editor Lung cancer Lung Neoplasms - genetics Lymphocytes MAP Kinase Signaling System Medical screening Minority & ethnic groups Mutation Neoplasms, Multiple Primary Patients R&D Research & development Survival analysis Tumors
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Summary:	In multiple primary lung cancers (MPLCs), surgery achieved a 5-year overall survival rate that varies from 27.4% to 95.8%.1 Targeted therapy has been applied to MPLC patients with different responses due to driver mutation heterogeneity.2 Meanwhile, two clinical trials are testing immune checkpoint inhibitors for MPLCs (NCT04026841; NCT04047186). Pathway analysis revealed that frequently altered genes during sMPLC development were centered around the Mitogen-Activated Protein Kinase/Extracellular-signal-Regulated Kinase (MAPK/ERK) pathway, including mutated downstream genes and altered upstream activators. [...]EGFR mutation in lung cancer has shown an association with a low objective response rate to PD-L1 inhibitors.9 Considering the generally EGFR-mutated, low PD-L1 expressed, low T-cell infiltrated profile, EGFR-TKI as the prior line of therapy may be a better option for the MPLC patient. PD-L1 inhibitor durvalumab demonstrated efficacy in treating heavily-pretreated EGFR+ advanced lung cancer patients in the ATLANTIC trial, although the objective response was lower than EGFR- group.10 Therefore, if the MPLC patient develops resistance to EGFR-TKIs, PD-L1 treatment may still be considered at the advanced stage In conclusion, our data revealed that the development of sMPLC went through MAPK/ERK pathway, which was first described in a large-scale MPLC sample size. [...]patients with EGFR-TKIs as maintenance therapy achieved a better DFS than patients with maintenance chemotherapy.
ISSN:	2001-1326 2001-1326