{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:25:46Z","timestamp":1790245546233,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15\u00a0months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16\u00a0months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyab048","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T20:12:45Z","timestamp":1615839165000},"page":"956-965","source":"Crossref","is-referenced-by-count":9,"title":["A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant <i>EGFR<\/i> and activated IGF1R"],"prefix":"10.1093","volume":"51","author":[{"given":"Go","family":"Makimoto","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichiro","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kubo","sequence":"additional","affiliation":[{"name":"Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sunami","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Kato","sequence":"additional","affiliation":[{"name":"Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan"},{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Ichihara","sequence":"additional","affiliation":[{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadoaki","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kammei","family":"Rai","sequence":"additional","affiliation":[{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan"},{"name":"Hospital-based Cancer Registry Division, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Hotta","sequence":"additional","affiliation":[{"name":"Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan"},{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tabata","sequence":"additional","affiliation":[{"name":"Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Kiura","sequence":"additional","affiliation":[{"name":"Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, 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