{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:04:48Z","timestamp":1790089488124,"version":"4.0.1"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Osimertinib, a third-generation EGFR-TKI, is effective for non-small cell lung cancer (NSCLC), but drug resistance significantly worsens patient outcomes. Epigenetic regulation, particularly methylation, is crucial in tumor progression and resistance development. Changes in polygenic methylation patterns are linked to osimertinib resistance in NSCLC, affecting drug target mutations, transporter functions, and signaling pathways. However, the mechanisms by which epigenetic regulation impacts NSCLC and drug resistance are not fully understood. This review summarizes the role of polygenic methylation in osimertinib resistance in NSCLC, examining its effects on drug targets, transporter functions, and signaling pathways. It systematically analyzes recent literature on how changes in DNA and RNA methylation patterns affect EGFR mutation status, drug transporter function, and intracellular signaling, providing a theoretical framework for understanding osimertinib resistance. Further research on the interaction between DNA methylation and other resistance mechanisms may lead to new treatment strategies and drug targets, enhancing efficacy and patient survival rates in NSCLC.<\/jats:p>","DOI":"10.3389\/fonc.2026.1943703","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:29:26Z","timestamp":1790087366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The methylation pattern of osimertinib resistance: prospects for diagnosis and treatment of NSCLC"],"prefix":"10.3389","volume":"16","author":[{"given":"Yiting","family":"He","sequence":"first","affiliation":[{"name":"Department of Pathology, Clinical Medical School of Jiujiang University","place":["Jiujiang, Jiangxi, China"]},{"name":"Jiujiang Clinical Precision Medicine Research Center","place":["Jiujiang, 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