{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:51:36Z","timestamp":1776844296079,"version":"3.51.2"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021-I2M-1-053"],"award-info":[{"award-number":["2021-I2M-1-053"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Human Cell"],"DOI":"10.1007\/s13577-025-01315-7","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:50:14Z","timestamp":1761655814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TPM3\u2013NTRK1 fusion confers resistance to osimertinib in lung adenocarcinoma: a model in a continuous cell line"],"prefix":"10.1007","volume":"38","author":[{"given":"Fang","family":"Cao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayin","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changsong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaocui","family":"Bian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-4982","authenticated-orcid":false,"given":"Yuqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"issue":"1","key":"1315_CR1","first-page":"10","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, et al. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10\u201345.","journal-title":"CA Cancer J Clin"},{"key":"1315_CR2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.semcancer.2017.11.019","volume":"52","author":"L Osmani","year":"2018","unstructured":"Osmani L, et al. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): moving from targeted therapy to immunotherapy. Semin Cancer Biol. 2018;52:103\u20139.","journal-title":"Semin Cancer Biol"},{"issue":"6","key":"1315_CR3","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1200\/JCO.21.01626","volume":"40","author":"AC Tan","year":"2022","unstructured":"Tan AC, Tan DSW. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol. 2022;40(6):611\u201325.","journal-title":"J Clin Oncol"},{"key":"1315_CR4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315056","author":"J Wu","year":"2022","unstructured":"Wu J, Lin Z. Non-small cell lung cancer targeted therapy: drugs and mechanisms of drug resistance. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms232315056.","journal-title":"Int J Mol Sci"},{"key":"1315_CR5","doi-asserted-by":"publisher","DOI":"10.69854\/jcq.2025.0024","author":"CZ Yang An","year":"2025","unstructured":"Yang An CZ, Zhuang X, Zheng X, Yasuda Y, Tang M. Emerging frontiers in the treatment of non-small cell lung cancer: innovations and clinical advances. J Clin Quest. 2025. https:\/\/doi.org\/10.69854\/jcq.2025.0024.","journal-title":"J Clin Quest"},{"issue":"7","key":"1315_CR6","doi-asserted-by":"publisher","first-page":"107006","DOI":"10.1016\/j.isci.2023.107006","volume":"26","author":"N Reischmann","year":"2023","unstructured":"Reischmann N, et al. Overcoming MET-mediated resistance in oncogene-driven NSCLC. iScience. 2023;26(7):107006.","journal-title":"iScience"},{"key":"1315_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14143337","author":"A Koulouris","year":"2022","unstructured":"Koulouris A, et al. Resistance to TKIs in EGFR-mutated non-small cell lung cancer: from mechanisms to new therapeutic strategies. Cancers (Basel). 2022. https:\/\/doi.org\/10.3390\/cancers14143337.","journal-title":"Cancers (Basel)"},{"issue":"3","key":"1315_CR8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.cllc.2019.09.004","volume":"21","author":"H Xia","year":"2020","unstructured":"Xia H, et al. Evidence of NTRK1 fusion as resistance mechanism to EGFR TKI in EGFR+ NSCLC: results from a large-scale survey of NTRK1 fusions in Chinese patients with lung cancer. Clin Lung Cancer. 2020;21(3):247\u201354.","journal-title":"Clin Lung Cancer"},{"issue":"4","key":"1315_CR9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrn1078","volume":"4","author":"MV Chao","year":"2003","unstructured":"Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003;4(4):299\u2013309.","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"1315_CR10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1158\/2159-8290.CD-14-0765","volume":"5","author":"A Vaishnavi","year":"2015","unstructured":"Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25\u201334.","journal-title":"Cancer Discov"},{"key":"1315_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.18.00183","volume":"2","author":"R Okamura","year":"2018","unstructured":"Okamura R, et al. Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics. JCO Precis Oncol. 2018;2:1\u201320.","journal-title":"JCO Precis Oncol"},{"issue":"1","key":"1315_CR12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41698-021-00206-y","volume":"5","author":"CB Westphalen","year":"2021","unstructured":"Westphalen CB, et al. Genomic context of NTRK1\/2\/3 fusion-positive tumours from a large real-world population. NPJ Precis Oncol. 2021;5(1):69.","journal-title":"NPJ Precis Oncol"},{"issue":"11","key":"1315_CR13","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1038\/nm.3352","volume":"19","author":"A Vaishnavi","year":"2013","unstructured":"Vaishnavi A, et al. Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013;19(11):1469\u201372.","journal-title":"Nat Med"},{"key":"1315_CR14","doi-asserted-by":"publisher","DOI":"10.1200\/po.18.00037","author":"AF Farago","year":"2018","unstructured":"Farago AF, et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018. https:\/\/doi.org\/10.1200\/po.18.00037.","journal-title":"JCO Precis Oncol"},{"issue":"6","key":"1315_CR15","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.cllc.2018.07.008","volume":"19","author":"E Helman","year":"2018","unstructured":"Helman E, et al. Cell-free DNA next-generation sequencing prediction of response and resistance to third-generation EGFR inhibitor. Clin Lung Cancer. 2018;19(6):518-530.e7.","journal-title":"Clin Lung Cancer"},{"issue":"4","key":"1315_CR16","doi-asserted-by":"publisher","first-page":"249","DOI":"10.6004\/jnccn.2204.0023","volume":"22","author":"GJ Riely","year":"2024","unstructured":"Riely GJ, et al. Non-small cell lung cancer, version 4.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2024;22(4):249\u201374.","journal-title":"J Natl Compr Canc Netw"},{"issue":"17","key":"1315_CR17","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1093\/jnci\/djq279","volume":"102","author":"AF Gazdar","year":"2010","unstructured":"Gazdar AF, et al. Lung cancer cell lines as tools for biomedical discovery and research. J Natl Cancer Inst. 2010;102(17):1310\u201321.","journal-title":"J Natl Cancer Inst"},{"key":"1315_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105369","volume":"119","author":"J Xu","year":"2021","unstructured":"Xu J, et al. Targeted DNA profiling and the prevalence of NTRK aberrations in Chinese patients with head and neck cancer. Oral Oncol. 2021;119:105369.","journal-title":"Oral Oncol"},{"issue":"11","key":"1315_CR19","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1097\/PAS.0000000000000911","volume":"41","author":"JF Hechtman","year":"2017","unstructured":"Hechtman JF, et al. Pan-Trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol. 2017;41(11):1547\u201351.","journal-title":"Am J Surg Pathol"},{"key":"1315_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2024.102733","volume":"127","author":"M Repetto","year":"2024","unstructured":"Repetto M, et al. NTRK gene fusion testing and management in lung cancer. Cancer Treat Rev. 2024;127:102733.","journal-title":"Cancer Treat Rev"},{"issue":"9","key":"1315_CR21","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/s41416-019-0573-8","volume":"121","author":"A Leonetti","year":"2019","unstructured":"Leonetti A, et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121(9):725\u201337.","journal-title":"Br J Cancer"},{"issue":"4","key":"1315_CR22","doi-asserted-by":"publisher","first-page":"258","DOI":"10.4132\/jptm.2016.04.19","volume":"50","author":"S Ahn","year":"2016","unstructured":"Ahn S, et al. Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases. J Pathol Transl Med. 2016;50(4):258\u201363.","journal-title":"J Pathol Transl Med"},{"issue":"11","key":"1315_CR23","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.trecan.2019.09.008","volume":"5","author":"VW Zhu","year":"2019","unstructured":"Zhu VW, Klempner SJ, Ou S-HI. Receptor tyrosine kinase fusions as an actionable resistance mechanism to EGFR TKIs in EGFR-mutant non-small-cell lung cancer. Trends Cancer. 2019;5(11):677\u201392.","journal-title":"Trends Cancer"},{"issue":"1","key":"1315_CR24","doi-asserted-by":"publisher","first-page":"1071","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. 2023;14(1):1071.","journal-title":"Nat Commun"},{"issue":"2","key":"1315_CR25","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3390\/cancers15020504","volume":"15","author":"H Chhouri","year":"2023","unstructured":"Chhouri H, Alexandre D, Grumolato L. Mechanisms of acquired resistance and tolerance to EGFR targeted therapy in non-small cell lung cancer. Cancers (Basel). 2023;15(2):504.","journal-title":"Cancers (Basel)"},{"issue":"1","key":"1315_CR26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13045-022-01391-4","volume":"15","author":"K Fu","year":"2022","unstructured":"Fu K, et al. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J Hematol Oncol. 2022;15(1):173.","journal-title":"J Hematol Oncol"},{"issue":"12","key":"1315_CR27","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","volume":"15","author":"E Cocco","year":"2018","unstructured":"Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol. 2018;15(12):731\u201347.","journal-title":"Nat Rev Clin Oncol"},{"issue":"7","key":"1315_CR28","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1093\/jnci\/djt007","volume":"105","author":"JP Gillet","year":"2013","unstructured":"Gillet JP, Varma S, Gottesman MM. The clinical relevance of cancer cell lines. J Natl Cancer Inst. 2013;105(7):452\u20138.","journal-title":"J Natl Cancer Inst"},{"key":"1315_CR29","first-page":"61","volume":"106","author":"H Rubin","year":"2001","unstructured":"Rubin H. Multistage carcinogenesis in cell culture. Dev Biol (Basel). 2001;106:61\u20136 (discussion 67, 143-60).","journal-title":"Dev Biol (Basel)"},{"issue":"23","key":"1315_CR30","first-page":"6863","volume":"48","author":"K Morikawa","year":"1988","unstructured":"Morikawa K, et al. Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice. Cancer Res. 1988;48(23):6863\u201371.","journal-title":"Cancer Res"},{"issue":"8","key":"1315_CR31","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.molonc.2014.06.001","volume":"8","author":"E Ardini","year":"2014","unstructured":"Ardini E, et al. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol Oncol. 2014;8(8):1495\u2013507.","journal-title":"Mol Oncol"},{"issue":"4","key":"1315_CR32","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1158\/1535-7163.MCT-15-0758","volume":"15","author":"E Ardini","year":"2016","unstructured":"Ardini E, et al. Entrectinib, a pan-TRK, ROS1, and ALK inhibitor with activity in multiple molecularly defined cancer indications. Mol Cancer Ther. 2016;15(4):628\u201339.","journal-title":"Mol Cancer Ther"},{"issue":"21","key":"1315_CR33","doi-asserted-by":"publisher","first-page":"6356","DOI":"10.7150\/jca.60845","volume":"12","author":"SH Sohn","year":"2021","unstructured":"Sohn SH, et al. TRK inhibitors block NFKB and induce NRF2 in TRK fusion-positive colon cancer. J Cancer. 2021;12(21):6356\u201362.","journal-title":"J Cancer"},{"issue":"10","key":"1315_CR34","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1158\/1078-0432.CCR-17-1623","volume":"24","author":"A Nishiyama","year":"2018","unstructured":"Nishiyama A, et al. Foretinib overcomes entrectinib resistance associated with the NTRK1 G667C mutation in NTRK1 fusion-positive tumor cells in a brain metastasis model. Clin Cancer Res. 2018;24(10):2357\u201369.","journal-title":"Clin Cancer Res"},{"issue":"12","key":"1315_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.7393","volume":"13","author":"Y Kato","year":"2024","unstructured":"Kato Y, et al. Induction of resistance to neurotrophic tropomyosin-receptor kinase inhibitors by HMGCS2 via a mevalonate pathway. Cancer Med. 2024;13(12):e7393.","journal-title":"Cancer Med"},{"issue":"10","key":"1315_CR36","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1158\/1535-7163.MCT-16-0909","volume":"16","author":"MJ Fuse","year":"2017","unstructured":"Fuse MJ, et al. Mechanisms of resistance to NTRK inhibitors and therapeutic strategies in NTRK1-rearranged cancers. Mol Cancer Ther. 2017;16(10):2130\u201343.","journal-title":"Mol Cancer Ther"},{"issue":"10","key":"1315_CR37","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1158\/2159-8290.CD-15-0443","volume":"5","author":"RC Doebele","year":"2015","unstructured":"Doebele RC, et al. An oncogenic NTRK fusion in a patient with soft-tissue sarcoma with response to the tropomyosin-related kinase inhibitor LOXO-101. Cancer Discov. 2015;5(10):1049\u201357.","journal-title":"Cancer Discov"},{"issue":"3","key":"1315_CR38","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/sj.leu.2404555","volume":"21","author":"TL Gu","year":"2007","unstructured":"Gu TL, et al. Phosphoproteomic analysis identifies the M0\u201391 cell line as a cellular model for the study of TEL-TRKC fusion-associated leukemia. Leukemia. 2007;21(3):563\u20136.","journal-title":"Leukemia"}],"container-title":["Human Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01315-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13577-025-01315-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-025-01315-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:50:15Z","timestamp":1761655815000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13577-025-01315-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["1315"],"URL":"https:\/\/doi.org\/10.1007\/s13577-025-01315-7","relation":{},"ISSN":["1749-0774"],"issn-type":[{"value":"1749-0774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"18 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Clinical sample was approved by the Ethics Committees of Perking University Cancer Hospital with informed consent obtained from the patient (approval number: 2024YJZ81-GZ01). All procedures were conducted in accordance with institutional and national ethical guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"182"}}