{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T22:40:36Z","timestamp":1762987236465,"version":"3.45.0"},"reference-count":27,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu Cancer Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jtocrr.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JTO Clinical and Research Reports"],"published-print":{"date-parts":[[2023,6]]},"DOI":"10.1016\/j.jtocrr.2023.100525","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T22:08:19Z","timestamp":1683842899000},"page":"100525","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors"],"prefix":"10.1016","volume":"4","author":[{"given":"Ryota","family":"Nakamura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadaaki","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Yaoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Miyagawa-Hayashino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Iwasaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsaku","family":"Tokuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Hak","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Konishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jtocrr.2023.100525_bib1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"10.1016\/j.jtocrr.2023.100525_bib2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jtocrr.2023.100525_bib3","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S1470-2045(19)30634-5","article-title":"Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"20","author":"Nakagawa","year":"2019","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib4","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/S1470-2045(17)30608-3","article-title":"Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial","volume":"18","author":"Wu","year":"2017","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1200\/JCO.19.01488","article-title":"Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study","volume":"38","author":"Hosomi","year":"2020","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib6","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1097\/JTO.0b013e31823ab0dd","article-title":"Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort","volume":"6","author":"Yano","year":"2011","journal-title":"J\u00a0Thorac Oncol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib7","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nm.2713","article-title":"A\u00a0common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer","volume":"18","author":"Ng","year":"2012","journal-title":"Nat Med"},{"key":"10.1016\/j.jtocrr.2023.100525_bib8","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41467-018-08074-0","article-title":"AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells","volume":"10","author":"Taniguchi","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.jtocrr.2023.100525_bib9","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1158\/1078-0432.CCR-19-2321","article-title":"ONO-7475, a novel AXL inhibitor, suppresses the adaptive resistance to initial EGFR-TKI treatment in EGFR-mutated non-small cell lung cancer","volume":"26","author":"Okura","year":"2020","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtocrr.2023.100525_bib10","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/cas.15608","article-title":"High levels of AXL expression in untreated EGFR-mutated non-small cell lung cancer negatively impacts the use of osimertinib","volume":"114","author":"Yoshimura","year":"2023","journal-title":"Cancer Sci"},{"key":"10.1016\/j.jtocrr.2023.100525_bib11","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1158\/2159-8290.CD-15-1283","article-title":"Tumor heterogeneity and lesion-specific response to targeted therapy in colorectal cancer","volume":"6","author":"Russo","year":"2016","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jtocrr.2023.100525_bib12","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1158\/2159-8290.CD-15-0748","article-title":"Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET-amplified esophagogastric cancer","volume":"5","author":"Kwak","year":"2015","journal-title":"Cancer Discov"},{"key":"10.1016\/j.jtocrr.2023.100525_bib13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature13948","article-title":"Convergent loss of PTEN leads to clinical resistance to a PI(3)K\u03b1 inhibitor","volume":"518","author":"Juric","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.jtocrr.2023.100525_bib14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.jtocrr.2023.100525_bib15","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41467-019-13771-5","article-title":"YAP1 mediates survival of ALK-rearranged lung cancer cells treated with alectinib via pro-apoptotic protein regulation","volume":"11","author":"Tsuji","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.jtocrr.2023.100525_bib16","doi-asserted-by":"crossref","DOI":"10.1038\/oncsis.2016.14","article-title":"A\u00a0HSP60-targeting peptide for cell apoptosis imaging","volume":"5","author":"Yang","year":"2016","journal-title":"Oncogenesis"},{"key":"10.1016\/j.jtocrr.2023.100525_bib17","doi-asserted-by":"crossref","first-page":"497","DOI":"10.6004\/jnccn.2022.0025","article-title":"Non-small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Ettinger","year":"2022","journal-title":"J\u00a0Natl Compr Canc Netw"},{"issue":"suppl 4","key":"10.1016\/j.jtocrr.2023.100525_bib18","doi-asserted-by":"crossref","first-page":"iv192","DOI":"10.1093\/annonc\/mdy275","article-title":"Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Planchard","year":"2018","journal-title":"Ann Oncol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib19","article-title":"Japanese lung cancer society guidelines for stage IV NSCLC with EGFR mutations","volume":"2","author":"Ninomiya","year":"2021","journal-title":"JTO Clin Res Rep"},{"key":"10.1016\/j.jtocrr.2023.100525_bib20","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/j.1349-7006.2008.00782.x","article-title":"Intratumor heterogeneity of epidermal growth factor receptor mutations in lung cancer and its correlation to the response to gefitinib","volume":"99","author":"Taniguchi","year":"2008","journal-title":"Cancer Sci"},{"key":"10.1016\/j.jtocrr.2023.100525_bib21","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nature12626","article-title":"Influence of tumour micro-environment heterogeneity on therapeutic response","volume":"501","author":"Junttila","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.jtocrr.2023.100525_bib22","doi-asserted-by":"crossref","first-page":"13373","DOI":"10.1073\/pnas.1404848111","article-title":"Direct regulation of GAS6\/AXL signaling by HIF promotes renal metastasis through SRC and MET","volume":"111","author":"Rankin","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jtocrr.2023.100525_bib23","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1158\/1078-0432.CCR-16-2586","article-title":"Integrative analysis identifies a novel AXL-PI3 kinase-PD-L1 signaling axis associated with radiation resistance in head and neck cancer","volume":"23","author":"Skinner","year":"2017","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jtocrr.2023.100525_bib24","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12943-019-0953-y","article-title":"Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas","volume":"18","author":"Tsukita","year":"2019","journal-title":"Mol Cancer"},{"key":"10.1016\/j.jtocrr.2023.100525_bib25","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jhep.2015.04.013","article-title":"Gas6\/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation","volume":"63","author":"B\u00e1rcena","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jtocrr.2023.100525_bib26","doi-asserted-by":"crossref","first-page":"5758","DOI":"10.1158\/0008-5472.CAN-19-1366","article-title":"S100A10 is a critical mediator of GAS6\/AXL-induced angiogenesis in renal cell carcinoma","volume":"79","author":"Xiao","year":"2019","journal-title":"Cancer Res"},{"key":"10.1016\/j.jtocrr.2023.100525_bib27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nm.4472","article-title":"Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF\/MEK inhibitors","volume":"24","author":"Boshuizen","year":"2018","journal-title":"Nat Med"}],"container-title":["JTO Clinical and Research Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666364323000644?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666364323000644?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T22:37:58Z","timestamp":1762987078000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666364323000644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["S2666364323000644"],"URL":"https:\/\/doi.org\/10.1016\/j.jtocrr.2023.100525","relation":{},"ISSN":["2666-3643"],"issn-type":[{"type":"print","value":"2666-3643"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors","name":"articletitle","label":"Article Title"},{"value":"JTO Clinical and Research Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jtocrr.2023.100525","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.","name":"copyright","label":"Copyright"}],"article-number":"100525"}}