{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:56:11Z","timestamp":1791262571849,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018071","name":"Knight Cancer Institute, Oregon Health and Science University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016943","name":"Prospect Creek Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016943","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["HG008100"],"award-info":[{"award-number":["HG008100"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000649","name":"Lady Margaret Hall, University of Oxford","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000649","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020527","name":"Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020527","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"National Institutes of Health Common Fund","doi-asserted-by":"publisher","award":["U54CA209988"],"award-info":[{"award-number":["U54CA209988"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society Inc","doi-asserted-by":"publisher","award":["RSG-22-060-01-MM"],"award-info":[{"award-number":["RSG-22-060-01-MM"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.celrep.2025.116826","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T08:14:19Z","timestamp":1767168859000},"page":"116826","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Growth factors maintain intratumoral heterogeneity and drive therapeutic resistance in triple-negative breast cancer"],"prefix":"10.1016","volume":"45","author":[{"given":"Kaylyn L.","family":"Devlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmar","family":"Bucher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe L.","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kilburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damir","family":"Sudar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi S.","family":"Feiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Heiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Langer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0030-6216","authenticated-orcid":false,"given":"James E.","family":"Korkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2025.116826_bib1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.ccell.2019.02.001","article-title":"Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies","volume":"35","author":"Jiang","year":"2019","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116826_bib2","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1056\/NEJMra1001389","article-title":"Triple-negative breast cancer","volume":"363","author":"Foulkes","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116826_bib3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"Yin","year":"2020","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.celrep.2025.116826_bib4","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1158\/1078-0432.CCR-06-1109","article-title":"The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes","volume":"13","author":"Carey","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116826_bib5","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116826_bib6","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1038\/s41467-018-06052-0","article-title":"Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq","volume":"9","author":"Karaayvaz","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.116826_bib7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-3-319-22909-6_7","article-title":"Intratumor Heterogeneity in Breast Cancer","volume":"882","author":"Beca","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.celrep.2025.116826_bib8","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.1172\/JCI60534","article-title":"Heterogeneity in breast cancer","volume":"121","author":"Polyak","year":"2011","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.celrep.2025.116826_bib9","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2011.07.026","article-title":"Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells","volume":"146","author":"Gupta","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116826_bib10","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1038\/s41467-018-05729-w","article-title":"Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer","volume":"9","author":"Risom","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.116826_bib11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccell.2020.03.007","article-title":"Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance","volume":"37","author":"Marusyk","year":"2020","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116826_bib12","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41591-021-01233-9","article-title":"Intratumoral heterogeneity in cancer progression and response to immunotherapy","volume":"27","author":"Vitale","year":"2021","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2025.116826_bib13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41422-023-00909-w","article-title":"ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer","volume":"34","author":"Ge","year":"2024","journal-title":"Cell Res."},{"key":"10.1016\/j.celrep.2025.116826_bib14","first-page":"3791","article-title":"Using Microarrays to Interrogate Microenvironmental Impact on Cellular Phenotypes in Cancer","volume":"10","author":"Smith","year":"2019","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.celrep.2025.116826_bib15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cels.2018.02.001","article-title":"Microenvironment-Mediated Mechanisms of Resistance to HER2 Inhibitors Differ between HER2+ Breast Cancer Subtypes","volume":"6","author":"Watson","year":"2018","journal-title":"Cell Syst."},{"key":"10.1016\/j.celrep.2025.116826_bib16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10549-024-07551-z","article-title":"Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795\/uprosertib in patients with metastatic triple negative breast cancer","volume":"210","author":"Prasath","year":"2025","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.celrep.2025.116826_bib17","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1056\/NEJMoa1210093","article-title":"Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations","volume":"367","author":"Flaherty","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116826_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/sdata.2017.166","article-title":"Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics","volume":"4","author":"Hafner","year":"2017","journal-title":"Sci. Data"},{"key":"10.1016\/j.celrep.2025.116826_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002585","article-title":"Single-Cell-Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process","volume":"14","author":"Richard","year":"2016","journal-title":"PLoS Biol."},{"key":"10.1016\/j.celrep.2025.116826_bib20","first-page":"1477","article-title":"Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases","volume":"11","author":"Rodig","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"10.1016\/j.celrep.2025.116826_bib21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116826_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116826_bib23","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1158\/0008-5472.CAN-08-3389","article-title":"Basal subtype and MAPK\/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition","volume":"69","author":"Mirzoeva","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.celrep.2025.116826_bib24","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1186\/bcr2594","article-title":"Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer","volume":"12","author":"Creighton","year":"2010","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.celrep.2025.116826_bib25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41568-022-00454-5","article-title":"Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer","volume":"22","author":"Labrie","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.celrep.2025.116826_bib26","doi-asserted-by":"crossref","first-page":"32977","DOI":"10.1074\/jbc.M105486200","article-title":"Dissociation of heparan sulfate and receptor binding domains of hepatocyte growth factor reveals that heparan sulfate-c-met interaction facilitates signaling","volume":"276","author":"Rubin","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2025.116826_bib27","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/bjc.2013.31","article-title":"High MET expression is an adverse prognostic factor in patients with triple-negative breast cancer","volume":"108","author":"Zagouri","year":"2013","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.celrep.2025.116826_bib28","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10549-013-2570-6","article-title":"HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients","volume":"139","author":"Bae","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"10.1016\/j.celrep.2025.116826_bib29","doi-asserted-by":"crossref","DOI":"10.1186\/bcr3480","article-title":"An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models","volume":"15","author":"Xia","year":"2013","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.celrep.2025.116826_bib30","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nature11249","article-title":"Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors","volume":"487","author":"Wilson","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116826_bib31","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/bioinformatics\/btr095","article-title":"Improved structure, function and compatibility for CellProfiler: modular high-throughput image analysis software","volume":"27","author":"Kamentsky","year":"2011","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2025.116826_bib38","volume":"2055","author":"Eng","year":"2020"},{"key":"10.1016\/j.celrep.2025.116826_bib32","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ccr.2006.10.008","article-title":"A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes","volume":"10","author":"Neve","year":"2006","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116826_bib33","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1073\/pnas.1018854108","article-title":"Subtype and pathway specific responses to anticancer compounds in breast cancer","volume":"109","author":"Heiser","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.116826_bib34","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1741-7015-7-77","article-title":"A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047","volume":"7","author":"Kuo","year":"2009","journal-title":"BMC Med."},{"key":"10.1016\/j.celrep.2025.116826_bib35","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nmeth.1896","article-title":"OMERO: flexible, model-driven data management for experimental biology","volume":"9","author":"Allan","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.celrep.2025.116826_bib36","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1080\/10618600.2020.1741379","article-title":"Automatic Transformation and Integration to Improve Visualization and Discovery of Latent Effects in Imaging Data","volume":"29","author":"Hunt","year":"2020","journal-title":"J. Comput. Graph Stat."},{"key":"10.1016\/j.celrep.2025.116826_bib37","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1093\/bioinformatics\/btac606","article-title":"Systematic replication enables normalization of high-throughput imaging assays","volume":"38","author":"Hunt","year":"2022","journal-title":"Bioinformatics"}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725015980?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725015980?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:44:16Z","timestamp":1791261856000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124725015980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S2211124725015980"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116826","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Growth factors maintain intratumoral heterogeneity and drive therapeutic resistance in triple-negative breast cancer","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116826","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"116826"}}