{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:12Z","timestamp":1785387612323,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["21K08187"],"award-info":[{"award-number":["21K08187"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23K07636"],"award-info":[{"award-number":["23K07636"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["23H02774"],"award-info":[{"award-number":["23H02774"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung cancer is the leading cause of cancer\u2010related deaths worldwide. Although osimertinib is more effective than previous\u2010generation drugs, its efficacy is often limited by both primary and acquired resistance. Cycling cancer persister cells (CPCs) have recently emerged as a transient, drug\u2010tolerant subpopulation that may contribute to early resistance to targeted therapies. However, their biological characteristics and role in osimertinib resistance remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We established osimertinib\u2010resistant CPCs derived from epidermal growth factor receptor (\n                      <jats:italic>EGFR)<\/jats:italic>\n                      \u2010mutant non\u2010small\u2010cell lung cancer (NSCLC) cell lines PC9 and HCC827. RNA sequencing (RNA\u2010seq) was performed to identify CPC\u2010specific transcriptional programs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNA\u2010seq analyses demonstrated that the tumor necrosis factor alpha (TNF\u2010\u03b1)\/nuclear factor\u2010\u03baB (NF\u2010\u03baB) signaling pathway was upregulated in osimertinib\u2010resistant PC9 cells (PC9\u2010CPCs), with interleukin\u20101 alpha (IL\u20101\u03b1) being the most significantly overexpressed gene. Treatment with IL\u20101\u03b1 increased TNF\u2010\u03b1 and NF\u2010\u03baB p65 expression in PC9 parental cells, whereas IL\u20101\u03b1 inhibition decreased TNF\u2010\u03b1 expression in PC9\u2010CPCs. Consequently, the inhibition of either IL\u20101\u03b1 or TNF\u2010\u03b1 restored the sensitivity of\n                      <jats:italic>EGFR<\/jats:italic>\n                      \u2010mutant NSCLC cells to osimertinib. Immunohistochemical analysis confirmed that NF\u2010\u03baB expression was higher in tumor specimens from patients who had developed osimertinib resistance than in specimens collected before treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CPCs exhibit a distinct inflammatory phenotype driven by IL\u20101\u03b1\u2013driven activation of the TNF\u2010\u03b1\/NF\u2010\u03baB axis, representing an alternative mechanism underlying osimertinib resistance. Targeting IL\u20101\u03b1 or TNF\u2010\u03b1 may provide a promising strategy to overcome resistance in patients with\n                      <jats:italic>EGFR<\/jats:italic>\n                      \u2010mutant NSCLC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70360","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T02:55:33Z","timestamp":1784343333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin\u20101\u03b1\u2010Mediated Activation of\n                    <scp>TNF<\/scp>\n                    \u2010\u03b1\/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Signaling Confers Resistance to Osimertinib in\n                    <scp>\n                      <i>EGFR<\/i>\n                    <\/scp>\n                    \u2010Mutant Non\u2010Small\u2010Cell Lung Cancer"],"prefix":"10.1111","volume":"17","author":[{"given":"Wira","family":"Winardi","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Juntendo University Faculty of Medicine and Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-6653","authenticated-orcid":false,"given":"Yoichiro","family":"Mitsuishi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Juntendo University Faculty of Medicine and Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8996-6167","authenticated-orcid":false,"given":"Hironari","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Juntendo University Faculty of Medicine and Graduate School of Medicine  Tokyo 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