{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:29:36Z","timestamp":1792416576836,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first\u2010 and second\u2010generation TKIs, third\u2010generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR\u2010driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the\n                    <jats:italic>EGFR T790M\/L858R<\/jats:italic>\n                    mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions.\n                  <\/jats:p>","DOI":"10.1002\/advs.202101999","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T21:22:46Z","timestamp":1633814566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cellular Origins of EGFR\u2010Driven Lung Cancer Cells Determine Sensitivity to Therapy"],"prefix":"10.1002","volume":"8","author":[{"given":"Fan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Toxicology and Cancer Biology University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Flight","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry University of Kentucky  Lexington KY 40536 USA"},{"name":"Markey Cancer Center University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassandra J.","family":"Naughton","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexsandr","family":"Lukyanchuk","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R.","family":"Edgin","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Cancer Biology University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"DNAtrix  10355 Science Center Drive, Suite 110 San Diego CA 92121 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok\u2010Kin","family":"Wong","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center New York University  New York NY 10016 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter N. 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