机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.四川大学华西医院[2]Department of Otolaryngology, Head and Neck Surgery, Chengdu Second People's Hospital, Chengdu, China.[3]Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.[4]Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[5]Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden.[6]Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.[7]Department of Thoracic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Tyrosine kinase inhibitor (TKI) treatment has significantly improved the prognosis of oncogenic-driven lung adenocarcinoma (LUAD). However, drug resistance limits the long-term benefits of patients. Therefore, there is a pressing need to explore the mechanism of TKI resistance and identify new therapeutic targets. It is possible to overcome TKI resistance by inducing tumor cell death through a new process called ferroptosis. Aberrations in ferroptosis, which is a kind of regulated cell death (RCD), has been confirmed to be involved in the development and progression of multiple tumors, and is closely related to patient survival. At present, the role of ferroptosis in TKI resistance remains unclear.Ferroptosis-related factors were isolated by expression characteristics analysis based on the multi-omics data of LUADs and normal lung tissues from The Cancer Genome Atlas (TCGA) database. Next, expression of selected ferroptosis-related factors and prognosis were analyzed. Subsequently, the differences in the expression of selected ferroptosis-related factors before and after TKI resistance on a variety of LUAD cell lines were analyzed to identify the factors that were involved in TKI resistance. Finally, the therapeutic effects were confirmed in vitro by targeting the selected ferroptosis-related factors with small molecule compounds.Glutathione Peroxidase 4 (GPX4), a ferroptosis-related factor, was up-regulated in tumor tissue of LUADs, and correlated with the prognosis of patients. By detecting the expression change of GPX4 before and after TKI resistance in a variety of LUAD cell lines, we confirmed that the inhibition of GPX4 could overcome epidermal growth factor receptor (EGFR)-TKI resistance by inducing ferroptosis.GPX4 could serve as a novel therapeutic target for EGFR-TKI resistance in LUAD.2022 Translational Lung Cancer Research. All rights reserved.
基金：
This work was supported by the 1.3.5 Project
for Disciplines of Excellence, West China Hospital,
Sichuan University (No. ZYGD18021 to Lunxu Liu, No.
ZYJC18009 to Jiandong Mei).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|3 区医学
小类|3 区呼吸系统4 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|3 区肿瘤学3 区呼吸系统
第一作者：
第一作者机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
通讯作者：
通讯机构：[1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.[*1]Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
推荐引用方式(GB/T 7714)：
Zhang Chuanfen,Wang Chunmei,Yang Zhenyu,et al.Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance.[J].Translational lung cancer research.2022,11(5):786-801.doi:10.21037/tlcr-22-318.
APA：
Zhang Chuanfen,Wang Chunmei,Yang Zhenyu,Bai Yuquan,Shukuya Takehito...&Deng Senyi.(2022).Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance..Translational lung cancer research,11,(5)
MLA：
Zhang Chuanfen,et al."Identification of GPX4 as a therapeutic target for lung adenocarcinoma after EGFR-TKI resistance.".Translational lung cancer research 11..5(2022):786-801
