Journal of Thoracic Oncology最新文献

{"title":"GSTA1 conferred tolerance to osimertinib and provided strategies to overcome drug-tolerant persister in EGFR-mutant lung adenocarcinoma.","authors":"Xiaoshen Zhang, Yaokai Wen, Fengying Wu, Yu Jiang, Yuechun Lin, Lei Wang, Fei Zhou, Yue Shen, Zhen Min, Wei Li, Wenhua Liang, Jianxing He, Caicun Zhou","doi":"10.1016/j.jtho.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.10.001","url":null,"abstract":"<p><p>The generation of drug-tolerant persister (DTP) cancer cells remains a major challenge for lung adenocarcinoma (LUAD) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), as these cells eventually lead to drug resistance and disease progression. However, the mechanisms underlying DTP formation are poorly understood, limiting treatment options when DTP state or resistance emerges following TKI therapy. In this study, utilizing samples from LUAD patients receiving front-line osimertinib therapy, including baseline, DTP, and stable resistance states, we dissected the cellular and transcriptomic features of TKI-induced DTP cells. These cells exhibited an active drug-metabolizing phenotype, characterized by significantly increased expression of Glutathione S-Transferase Alpha 1 (GSTA1), which was regulated by Radial Spoke Head Component 1 (RSPH1). Mechanistically, we demonstrated that elevated GSTA1 expression in cancer cells promoted osimertinib degradation. Furthermore, RSPH1+ DTP cells interacted with macrophages via Protein S (PROS1)-AXL signaling to establish an immunosuppressive tumor microenvironment (TME), thereby contributing to persister formation. We investigated the RSPH1-CALML4-GSTA1 regulatory axis and found that PROS1 expression was also governed by this axis, suggesting that GSTA1 acted as an upstream regulator of the PROS1-AXL signaling pathway. We evaluated the feasibility of combination therapy using osimertinib and the GSTA1 inhibitor curzerene in both osimertinib-induced DTP and acquired resistance mouse models. Notably, this strategy demonstrated superior efficacy and safety compared to chemotherapy or AXL inhibitor combination in both settings. Collectively, our study elucidated novel mechanisms contributing to the TKI-induced DTP state and provided a promising combination strategy to overcome drug tolerance and resistance in osimertinib-treated LUAD patients.</p>","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to 'Gut Microbiota in Advanced NSCLC Receiving Chemoimmunotherapy: An Ancillary Biomarker Study From the Phase III Trial JCOG2007 (NIPPON)' [Journal of Thoracic Oncology Vol. 20 No. 7 (2025) 912-927].","authors":"Taiki Hakozaki, Kentaro Tanaka, Yoshimasa Shiraishi, Yuta Sekino, Noriko Mitome, Yusuke Okuma, Tomoiki Aiba, Takahiro Utsumi, Junko Tanizaki, Koichi Azuma, Satoshi Hara, Ryo Morita, Seiji Niho, Toshihide Yokoyama, Ryo Toyozawa, Hidehito Horinouchi, Isamu Okamoto, Yukio Hosomi, Yuichiro Ohe","doi":"10.1016/j.jtho.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.jtho.2025.09.004","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":" ","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Impact of Comorbidities on Lung Cancer Screening Mortality Benefits: Insights and Suggestions for Methodological Enhancement","authors":"Yimao Wu MD,&nbsp;Yalun Liang MD,&nbsp;Jintao Liang MD","doi":"10.1016/j.jtho.2025.06.004","DOIUrl":"10.1016/j.jtho.2025.06.004","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e111-e112"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“WEE”ding Out Resistance to Osimertinib in the “ARID”1A-Mutated Badlands","authors":"Steven G. Gray PhD ,&nbsp;Luciano Mutti MD","doi":"10.1016/j.jtho.2025.07.120","DOIUrl":"10.1016/j.jtho.2025.07.120","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages 1366-1368"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical Considerations for the Evaluation of Lazertinib in NSCLC With Uncommon EGFR Mutations","authors":"Xuefan Zeng MD,&nbsp;Qian Guo MD","doi":"10.1016/j.jtho.2025.05.025","DOIUrl":"10.1016/j.jtho.2025.05.025","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e105-e106"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors or Blocking Antibodies? Unraveling Vascular Endothelial Growth Factor Inhibition Strategies","authors":"Daphne W. Dumoulin MD,&nbsp;G. Joachim V. Aerts MD, PhD","doi":"10.1016/j.jtho.2025.07.012","DOIUrl":"10.1016/j.jtho.2025.07.012","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages 1359-1361"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable Benefit Beyond Response: Reinterpreting Amivantamab Efficacy in METex14 NSCLC Subgroups","authors":"Tsai Ling Ting MSc,&nbsp;Shiuan-Chih Chen MD, PhD","doi":"10.1016/j.jtho.2025.06.006","DOIUrl":"10.1016/j.jtho.2025.06.006","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e108-e109"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for Lung Cancer, Overdiagnosis, and Health Care Utilization: A Nationwide Population-Based Study","authors":"Defeng Zhao MD,&nbsp;Wenze Li PhD,&nbsp;Wenya Li MD, PhD","doi":"10.1016/j.jtho.2025.06.003","DOIUrl":"10.1016/j.jtho.2025.06.003","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e114-e115"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to Letter to the Editor: “Screening for Lung Cancer, Overdiagnosis, and Healthcare Utilization: A Nationwide Population-Based Study”","authors":"So Yeon Kim MD, MS,&nbsp;Gerard A. Silvestri MD, MS,&nbsp;Young Sik Park MD, PhD","doi":"10.1016/j.jtho.2025.07.123","DOIUrl":"10.1016/j.jtho.2025.07.123","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e115-e116"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Response to the Letter to the Editor Regarding “Lazertinib for Patients With NSCLC Harboring Uncommon EGFR Mutations”","authors":"Min Hee Hong MD","doi":"10.1016/j.jtho.2025.07.126","DOIUrl":"10.1016/j.jtho.2025.07.126","url":null,"abstract":"","PeriodicalId":17515,"journal":{"name":"Journal of Thoracic Oncology","volume":"20 10","pages":"Pages e107-e108"},"PeriodicalIF":20.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}