{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:25:50Z","timestamp":1793802350088,"version":"4.6.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19cm0106206h0004, 20gm1210001, 21cm0106576h0002, 23ck0106722h0002"],"award-info":[{"award-number":["19cm0106206h0004, 20gm1210001, 21cm0106576h0002, 23ck0106722h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009024","name":"MEXT | JST | Exploratory Research for Advanced Technology","doi-asserted-by":"publisher","award":["JPMJER2303"],"award-info":[{"award-number":["JPMJER2303"]}],"id":[{"id":"10.13039\/501100009024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008965","name":"Takahashi Industrial and Economic Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-59623-3","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T13:02:53Z","timestamp":1746968573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Basal-shift transformation leads to EGFR therapy-resistance in human lung adenocarcinoma"],"prefix":"10.1038","volume":"16","author":[{"given":"Taro","family":"Shinozaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Togasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Mitsuishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sugihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Ebisudani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Shigematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatsuyo","family":"Takaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumimaro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ohgino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Ishioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kageaki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunekazu","family":"Hishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-0851","authenticated-orcid":false,"given":"Yutaka","family":"Kurebayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4842-8116","authenticated-orcid":false,"given":"Katsura","family":"Emoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-1930","authenticated-orcid":false,"given":"Hideki","family":"Terai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinnosuke","family":"Ikemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Kawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Asakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Hishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisao","family":"Asamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-2117","authenticated-orcid":false,"given":"Sirirat","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-7076","authenticated-orcid":false,"given":"Mayumi","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumu","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Matano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-995X","authenticated-orcid":false,"given":"Kenzo","family":"Soejima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-3943","authenticated-orcid":false,"given":"Masayuki","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Fukunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-8137","authenticated-orcid":false,"given":"Toshiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"59623_CR1","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1126\/science.1099314","volume":"304","author":"JG Paez","year":"2004","unstructured":"Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497\u20131500 (2004).","journal-title":"Science"},{"key":"59623_CR2","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1056\/NEJMoa040938","volume":"350","author":"TJ Lynch","year":"2004","unstructured":"Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129\u20132139 (2004).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR3","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1056\/NEJMoa0810699","volume":"361","author":"TS Mok","year":"2009","unstructured":"Mok, T. S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361, 947\u2013957 (2009).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S1470-2045(11)70393-X","volume":"13","author":"R Rosell","year":"2012","unstructured":"Rosell, R. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13, 239\u2013246 (2012).","journal-title":"Lancet Oncol."},{"key":"59623_CR5","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1200\/JCO.2012.44.2806","volume":"31","author":"LV Sequist","year":"2013","unstructured":"Sequist, L. V. et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J. Clin. Oncol. 31, 3327\u20133334 (2013).","journal-title":"J. Clin. Oncol."},{"key":"59623_CR6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","volume":"378","author":"JC Soria","year":"2018","unstructured":"Soria, J. C. et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N. Engl. J. Med. 378, 113\u2013125 (2018).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR7","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1056\/NEJMoa044238","volume":"352","author":"S Kobayashi","year":"2005","unstructured":"Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786\u2013792 (2005).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR8","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","volume":"376","author":"TS Mok","year":"2017","unstructured":"Mok, T. S. et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N. Engl. J. Med. 376, 629\u2013640 (2017).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR9","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1158\/2159-8290.CD-14-0337","volume":"4","author":"DA Cross","year":"2014","unstructured":"Cross, D. A. et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 4, 1046\u20131061 (2014).","journal-title":"Cancer Discov."},{"key":"59623_CR10","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1038\/ng.3990","volume":"49","author":"CM Blakely","year":"2017","unstructured":"Blakely, C. M. et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat. Genet. 49, 1693\u20131704 (2017).","journal-title":"Nat. Genet."},{"key":"59623_CR11","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s43018-021-00195-8","volume":"2","author":"A Passaro","year":"2021","unstructured":"Passaro, A., Janne, P. A., Mok, T. & Peters, S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat. Cancer 2, 377\u2013391 (2021).","journal-title":"Nat. Cancer"},{"key":"59623_CR12","doi-asserted-by":"crossref","unstructured":"Piper-Vallillo, A. J., Sequist, L. V. & Piotrowska, Z. Emerging Treatment Paradigms for EGFR-Mutant Lung Cancers Progressing on Osimertinib: A Review. J. Clin. Oncol. 38, 2926\u20132936 (2020).","DOI":"10.1200\/JCO.19.03123"},{"key":"59623_CR13","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1158\/2159-8290.CD-18-1022","volume":"8","author":"Z Piotrowska","year":"2018","unstructured":"Piotrowska, Z. et al. Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. Cancer Discov. 8, 1529\u20131539 (2018).","journal-title":"Cancer Discov."},{"key":"59623_CR14","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1001\/jamaoncol.2018.2969","volume":"4","author":"GR Oxnard","year":"2018","unstructured":"Oxnard, G. R. et al. Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. 4, 1527\u20131534 (2018).","journal-title":"JAMA Oncol."},{"key":"59623_CR15","doi-asserted-by":"publisher","first-page":"6195","DOI":"10.1158\/1078-0432.CCR-18-1542","volume":"24","author":"X Le","year":"2018","unstructured":"Le, X. et al. Landscape of EGFR-dependent and -independent resistance mechanisms to osimertinib and continuation therapy beyond progression in EGFR-mutant NSCLC. Clin. Cancer Res. 24, 6195\u20136203 (2018).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35962-x","volume":"14","author":"J Chmielecki","year":"2023","unstructured":"Chmielecki, J. et al. Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial. Nat. Commun. 14, 1071 (2023).","journal-title":"Nat. Commun."},{"key":"59623_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35961-y","volume":"14","author":"J Chmielecki","year":"2023","unstructured":"Chmielecki, J. et al. Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer. Nat. Commun. 14, 1070 (2023).","journal-title":"Nat. Commun."},{"key":"59623_CR18","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1158\/1078-0432.CCR-18-3829","volume":"25","author":"BP Brown","year":"2019","unstructured":"Brown, B. P. et al. On-target resistance to the mutant-selective EGFR inhibitor osimertinib can develop in an allele-specific manner dependent on the original EGFR-activating mutation. Clin. Cancer Res. 25, 3341\u20133351 (2019).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07078-0","volume":"9","author":"J Fassunke","year":"2018","unstructured":"Fassunke, J. et al. Overcoming EGFR(G724S)-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors. Nat. Commun. 9, 4655 (2018).","journal-title":"Nat. Commun."},{"key":"59623_CR20","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/nm.3854","volume":"21","author":"KS Thress","year":"2015","unstructured":"Thress, K. S. et al. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat. Med. 21, 560\u2013562 (2015).","journal-title":"Nat. Med."},{"key":"59623_CR21","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1158\/1078-0432.CCR-15-0560","volume":"21","author":"MJ Niederst","year":"2015","unstructured":"Niederst, M. J. et al. The allelic context of the C797S mutation acquired upon treatment with third-generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies. Clin. Cancer Res. 21, 3924\u20133933 (2015).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR22","doi-asserted-by":"publisher","first-page":"e226","DOI":"10.1016\/j.jtho.2019.05.046","volume":"14","author":"I Dagogo-Jack","year":"2019","unstructured":"Dagogo-Jack, I. et al. Response to the combination of osimertinib and trametinib in a patient with EGFR-mutant NSCLC harboring an acquired BRAF fusion. J. Thorac. Oncol. 14, e226\u2013e228 (2019).","journal-title":"J. Thorac. Oncol."},{"key":"59623_CR23","doi-asserted-by":"publisher","first-page":"3097","DOI":"10.1158\/1078-0432.CCR-17-2310","volume":"24","author":"Z Yang","year":"2018","unstructured":"Yang, Z. et al. Investigating novel resistance mechanisms to third-generation EGFR tyrosine kinase inhibitor osimertinib in non-small cell lung cancer patients. Clin. Cancer Res. 24, 3097\u20133107 (2018).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18442-4","volume":"11","author":"R Wang","year":"2020","unstructured":"Wang, R. et al. Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer. Nat. Commun. 11, 4607 (2020).","journal-title":"Nat. Commun."},{"key":"59623_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-08074-0","volume":"10","author":"H Taniguchi","year":"2019","unstructured":"Taniguchi, H. et al. AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells. Nat. Commun. 10, 259 (2019).","journal-title":"Nat. Commun."},{"key":"59623_CR26","unstructured":"Offin, M., et al. Acquired ALK and RET gene fusions as mechanisms of resistance to osimertinib in EGFR-mutant lung cancers. JCO Precis. Oncol. 2, PO.18.00126 (2018)."},{"key":"59623_CR27","doi-asserted-by":"publisher","first-page":"3916","DOI":"10.1158\/0008-5472.CAN-20-4048","volume":"81","author":"K Ishioka","year":"2021","unstructured":"Ishioka, K. et al. Upregulation of FGF9 in lung adenocarcinoma transdifferentiation to small cell lung cancer. Cancer Res. 81, 3916\u20133929 (2021).","journal-title":"Cancer Res."},{"key":"59623_CR28","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1158\/1078-0432.CCR-19-3563","volume":"26","author":"AJ Schoenfeld","year":"2020","unstructured":"Schoenfeld, A. J. et al. Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in EGFR-mutant lung cancer. Clin. Cancer Res. 26, 2654\u20132663 (2020).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR29","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.cell.2020.07.017","volume":"182","author":"A Maynard","year":"2020","unstructured":"Maynard, A. et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell 182, 1232\u20131251 e1222 (2020).","journal-title":"Cell"},{"key":"59623_CR30","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.1158\/0008-5472.CAN-20-2811","volume":"81","author":"Y Kashima","year":"2021","unstructured":"Kashima, Y. et al. Single-cell analyses reveal diverse mechanisms of resistance to EGFR tyrosine kinase inhibitors in lung cancer. Cancer Res. 81, 4835\u20134848 (2021).","journal-title":"Cancer Res."},{"key":"59623_CR31","doi-asserted-by":"crossref","unstructured":"Nilsson, M. B. et al. A YAP\/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components. Sci. Transl. Med. 12, eaaz4589 (2020).","DOI":"10.1126\/scitranslmed.aaz4589"},{"key":"59623_CR32","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41591-018-0264-7","volume":"25","author":"KN Shah","year":"2019","unstructured":"Shah, K. N. et al. Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer. Nat. Med. 25, 111\u2013118 (2019).","journal-title":"Nat. Med"},{"key":"59623_CR33","unstructured":"Sachs, N., et al. Long-term expanding human airway organoids for disease modeling. EMBO J. 38, e100300 (2019)."},{"key":"59623_CR34","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.1158\/1078-0432.CCR-20-5026","volume":"27","author":"SY Kim","year":"2021","unstructured":"Kim, S. Y. et al. Modeling clinical responses to targeted therapies by patient-derived organoids of advanced lung adenocarcinoma. Clin. Cancer Res. 27, 4397\u20134409 (2021).","journal-title":"Clin. Cancer Res."},{"key":"59623_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11867-6","volume":"10","author":"M Kim","year":"2019","unstructured":"Kim, M. et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat. Commun. 10, 3991 (2019).","journal-title":"Nat. Commun."},{"key":"59623_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107588","volume":"31","author":"KK Dijkstra","year":"2020","unstructured":"Dijkstra, K. K. et al. Challenges in establishing pure lung cancer organoids limit their utility for personalized medicine. Cell Rep. 31, 107588 (2020).","journal-title":"Cell Rep."},{"key":"59623_CR37","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1158\/1078-0432.CCR-19-1376","volume":"26","author":"R Shi","year":"2020","unstructured":"Shi, R. et al. Organoid cultures as preclinical models of non-small cell lung cancer. Clin. Cancer Res 26, 1162\u20131174 (2020).","journal-title":"Clin. Cancer Res"},{"key":"59623_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112212","volume":"42","author":"T Ebisudani","year":"2023","unstructured":"Ebisudani, T. et al. Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma. Cell Rep. 42, 112212 (2023).","journal-title":"Cell Rep."},{"key":"59623_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100911","volume":"4","author":"HM Wang","year":"2023","unstructured":"Wang, H. M. et al. Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study. Cell Rep. Med. 4, 100911 (2023).","journal-title":"Cell Rep. Med."},{"key":"59623_CR40","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nature13385","volume":"511","author":"Cancer Genome Atlas Research, N.","year":"2014","unstructured":"Cancer Genome Atlas Research, N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543\u2013550 (2014).","journal-title":"Nature"},{"key":"59623_CR41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nature14664","volume":"524","author":"J George","year":"2015","unstructured":"George, J. et al. Comprehensive genomic profiles of small cell lung cancer. Nature 524, 47\u201353 (2015).","journal-title":"Nature"},{"key":"59623_CR42","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41568-019-0133-9","volume":"19","author":"CM Rudin","year":"2019","unstructured":"Rudin, C. M. et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat. Rev. Cancer 19, 289\u2013297 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"59623_CR43","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41589-022-00984-x","volume":"18","author":"K Toshimitsu","year":"2022","unstructured":"Toshimitsu, K. et al. Organoid screening reveals epigenetic vulnerabilities in human colorectal cancer. Nat. Chem. Biol. 18, 605\u2013614 (2022).","journal-title":"Nat. Chem. Biol."},{"key":"59623_CR44","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.ccell.2021.07.020","volume":"39","author":"V Veninga","year":"2021","unstructured":"Veninga, V. & Voest, E. E. Tumor organoids: opportunities and challenges to guide precision medicine. Cancer Cell 39, 1190\u20131201 (2021).","journal-title":"Cancer Cell"},{"key":"59623_CR45","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.stem.2018.11.016","volume":"23","author":"M Fujii","year":"2018","unstructured":"Fujii, M. et al. Human intestinal organoids maintain self-renewal capacity and cellular diversity in niche-inspired culture condition. Cell Stem Cell 23, 787\u2013793.e786 (2018).","journal-title":"Cell Stem Cell"},{"key":"59623_CR46","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.stem.2017.12.009","volume":"22","author":"T Seino","year":"2018","unstructured":"Seino, T. et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 22, 454\u2013467.e456 (2018).","journal-title":"Cell Stem Cell"},{"key":"59623_CR47","doi-asserted-by":"crossref","unstructured":"Tamagawa, H. et al. Wnt-deficient and hypoxic environment orchestrates squamous reprogramming of human pancreatic ductal adenocarcinoma. Nat. Cell Biol. 26, 1759\u20131772 (2024).","DOI":"10.1038\/s41556-024-01498-5"},{"key":"59623_CR48","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwad028","volume":"10","author":"S Tang","year":"2023","unstructured":"Tang, S. et al. Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment. Natl Sci. Rev. 10, nwad028 (2023).","journal-title":"Natl Sci. Rev."},{"key":"59623_CR49","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1056\/NEJMoa1505270","volume":"373","author":"NC Turner","year":"2015","unstructured":"Turner, N. C., Huang Bartlett, C. & Cristofanilli, M. Palbociclib in hormone-receptor-positive advanced breast cancer. N. Engl. J. Med. 373, 1672\u20131673 (2015).","journal-title":"N. Engl. J. Med."},{"key":"59623_CR50","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1200\/JCO.21.02742","volume":"40","author":"M Royce","year":"2022","unstructured":"Royce, M. et al. FDA approval summary: abemaciclib with endocrine therapy for high-risk early breast cancer. J. Clin. Oncol. 40, 1155\u20131162 (2022).","journal-title":"J. Clin. Oncol."},{"key":"59623_CR51","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1200\/PO.20.00037","volume":"4","author":"ER Ahn","year":"2020","unstructured":"Ahn, E. R. et al. Palbociclib in patients with non-small-cell lung cancer with CDKN2A alterations: results from the targeted agent and profiling utilization registry study. JCO Precis Oncol. 4, 757\u2013766 (2020).","journal-title":"JCO Precis Oncol."},{"key":"59623_CR52","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/j.jtho.2019.06.027","volume":"14","author":"MJ Edelman","year":"2019","unstructured":"Edelman, M. J. et al. SWOG S1400C (NCT02154490)-a phase II study of palbociclib for previously treated cell cycle gene alteration-positive patients with stage IV squamous cell lung cancer (lung-MAP substudy). J. Thorac. Oncol. 14, 1853\u20131859 (2019).","journal-title":"J. Thorac. Oncol."},{"key":"59623_CR53","doi-asserted-by":"crossref","unstructured":"Mihara, E. et al. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin\/alpha-albumin. Elife 5, e11621 (2016).","DOI":"10.7554\/eLife.11621"},{"key":"59623_CR54","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.cell.2020.10.023","volume":"183","author":"K Kawasaki","year":"2020","unstructured":"Kawasaki, K. et al. An organoid biobank of neuroendocrine neoplasms enables genotype-phenotype mapping. Cell 183, 1420\u20131435.e1421 (2020).","journal-title":"Cell"},{"key":"59623_CR55","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"59623_CR56","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"59623_CR57","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinforma. 12, 323 (2011).","journal-title":"BMC Bioinforma."},{"key":"59623_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"59623_CR59","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1093\/bioinformatics\/btq170","volume":"26","author":"MD Wilkerson","year":"2010","unstructured":"Wilkerson, M. D. & Hayes, D. N. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 26, 1572\u20131573 (2010).","journal-title":"Bioinformatics"},{"key":"59623_CR60","doi-asserted-by":"publisher","first-page":"23981","DOI":"10.1074\/jbc.M702044200","volume":"282","author":"JW Tullai","year":"2007","unstructured":"Tullai, J. W. et al. Immediate-early and delayed primary response genes are distinct in function and genomic architecture. J. Biol. Chem. 282, 23981\u201323995 (2007).","journal-title":"J. Biol. Chem."},{"key":"59623_CR61","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"59623_CR62","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289\u20131296 (2019).","journal-title":"Nat. Methods"},{"key":"59623_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0","volume":"19","author":"K Street","year":"2018","unstructured":"Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).","journal-title":"BMC Genomics"},{"key":"59623_CR64","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"},{"key":"59623_CR65","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/nmeth.4396","volume":"14","author":"MR Corces","year":"2017","unstructured":"Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959\u2013962 (2017).","journal-title":"Nat. Methods"},{"key":"59623_CR66","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"59623_CR67","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).","journal-title":"Genome Biol."},{"key":"59623_CR68","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576\u2013589 (2010).","journal-title":"Mol. Cell"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59623-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59623-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59623-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T01:02:53Z","timestamp":1747357373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59623-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,11]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["59623"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-59623-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,11]]},"assertion":[{"value":"14 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"T.S. is an inventor on several patents related to organoid culture. We declare that none of the authors have competing financial or non-financial interests as defined by Nature Portfolio.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4369"}}