{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:21:11Z","timestamp":1792092071295,"version":"4.4.0"},"reference-count":60,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been developed to treat non-small cell lung cancer (NSCLC) patients with EGFR mutation, but TKI resistance is common. Almost half of the acquired resistance patients are due to additional T790M mutation on EGFR (EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    ), thus overcoming TKI resistance is important. In this study, we aim to investigate the role of reactive oxygen species (ROS) in TKI resistance as well as the molecular and biological effects of EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    after redox manipulation.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    The basal ROS levels in EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    -containing TKI-resistant NSCLC cell lines were substantially high. Sixty-three human lung tumors showed higher NADPH oxidase isoform 2 (NOX2) expression than normal lung tissues, which may contribute to high basal ROS in cancer and poor survival. Interestingly, only NOX3 was upregulated by sanguinarine, a pharmacological agent to elevate ROS, and resulted in EGFR overoxidation, degradation, and apoptosis. By contrast, such responses were lacking in EGFR\n                    <jats:sup>WT<\/jats:sup>\n                    cells. Selective EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    degradation was manipulated by redox imbalance between NOX3 and methionine reductase A (MsrA). Furthermore, the\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    tumor suppression effect of sanguinarine, NOX3 upregulation, and EGFR degradation were confirmed.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    We have found a new treatment strategy to overcome TKI resistance by selectively inducing EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    degradation\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    specific stimulation of methionine 790 (M790) oxidation. It can be achieved\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    manipulating redox imbalance between NOX3 and MsrA.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    Targeting EGFR by elevating ROS and redox imbalance is a potential new strategy to develop a new EGFR inhibitor for TKI-resistant patients with a wide therapeutic window between EGFR\n                    <jats:sup>T790M<\/jats:sup>\n                    and EGFR\n                    <jats:sup>WT<\/jats:sup>\n                    .\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    24, 263\u2013279.\n                  <\/jats:p>","DOI":"10.1089\/ars.2015.6420","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T13:01:58Z","timestamp":1446555718000},"page":"263-279","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":76,"title":["Targeting Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer by Inducing Epidermal Growth Factor Receptor Degradation\n                    <i>via<\/i>\n                    Methionine 790 Oxidation"],"prefix":"10.1177","volume":"24","author":[{"given":"Elaine Lai-Han","family":"Leung","sequence":"first","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pik","family":"Wong","sequence":"additional","affiliation":[{"name":"University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Qiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Fong","family":"Yau","sequence":"additional","affiliation":[{"name":"Macau University of Science and Technology","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky Pui-Chi","family":"Tin","sequence":"additional","affiliation":[{"name":"University of Hong Kong","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Macau University of Science and 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