{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:40:05Z","timestamp":1789767605308,"version":"4.0.1"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-52694-8","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T15:25:20Z","timestamp":1727882720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular and functional landscape of malignant serous effusions for precision oncology"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-3303","authenticated-orcid":false,"given":"Rebekka","family":"Wegmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4650-7830","authenticated-orcid":false,"given":"Lorenz","family":"Bankel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Festl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohyon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Cappelletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7818-5297","authenticated-orcid":false,"given":"Aaron","family":"Fehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Picotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin J.","family":"Dedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Franzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-9854","authenticated-orcid":false,"given":"Daniela","family":"Lenggenhager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K.","family":"Bode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0421-7229","authenticated-orcid":false,"given":"Martin","family":"Zoche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2839","authenticated-orcid":false,"given":"Holger","family":"Moch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Britschgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3386-6583","authenticated-orcid":false,"given":"Berend","family":"Snijder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"52694_CR1","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/S0140-6736(14)61396-9","volume":"385","author":"M Quaresma","year":"2015","unstructured":"Quaresma, M., Coleman, M. P. & Rachet, B. 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales, 1971\u20132011: a population-based study. Lancet 385, 1206\u20131218 (2015).","journal-title":"Lancet"},{"key":"52694_CR2","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1016\/S1470-2045(19)30456-5","volume":"20","author":"M Arnold","year":"2019","unstructured":"Arnold, M. et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995\u20132014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 20, 1493\u20131505 (2019).","journal-title":"Lancet Oncol."},{"key":"52694_CR3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41573-021-00301-6","volume":"21","author":"A Honkala","year":"2021","unstructured":"Honkala, A., Malhotra, S. V., Kummar, S. & Junttila, M. R. Harnessing the predictive power of preclinical models for oncology drug development. Nat. Rev. Drug Discov. 21, 99\u2013114 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"52694_CR4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/s41573-021-00252-y","volume":"20","author":"MM Attwood","year":"2021","unstructured":"Attwood, M. M., Fabbro, D., Sokolov, A. V., Knapp, S. & Schi\u00f6th, H. B. Trends in kinase drug discovery: targets, indications and inhibitor design. Nat. Rev. Drug Discov. 20, 839\u2013861 (2021).","journal-title":"Nat. Rev. Drug Discov."},{"key":"52694_CR5","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1126\/science.3798106","volume":"235","author":"DJ Slamon","year":"1987","unstructured":"Slamon, D. J. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2\/neu oncogene. Science 235, 177\u2013182 (1987).","journal-title":"Science"},{"key":"52694_CR6","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1056\/NEJMoa1703643","volume":"377","author":"G von Minckwitz","year":"2017","unstructured":"von Minckwitz, G. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N. Engl. J. Med. 377, 122\u2013131 (2017).","journal-title":"N. Engl. J. Med."},{"key":"52694_CR7","doi-asserted-by":"publisher","first-page":"e214","DOI":"10.1634\/theoncologist.2019-0446","volume":"25","author":"D Tripathy","year":"2020","unstructured":"Tripathy, D. et al. De novo versus recurrent HER2-positive metastatic breast cancer: patient characteristics, treatment, and survival from the SystHERs registry. Oncologist 25, e214\u2013e222 (2020).","journal-title":"Oncologist"},{"key":"52694_CR8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1002011","volume":"363","author":"KT Flaherty","year":"2010","unstructured":"Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809\u2013819 (2010).","journal-title":"N. Engl. J. Med."},{"key":"52694_CR9","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1056\/NEJMoa1210093","volume":"367","author":"KT Flaherty","year":"2012","unstructured":"Flaherty, K. T. et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694\u20131703 (2012).","journal-title":"N. Engl. J. Med."},{"key":"52694_CR10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1056\/NEJMoa1412690","volume":"372","author":"C Robert","year":"2015","unstructured":"Robert, C. et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372, 30\u201339 (2015).","journal-title":"N. Engl. J. Med."},{"key":"52694_CR11","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1016\/S1470-2045(18)30497-2","volume":"19","author":"R Dummer","year":"2018","unstructured":"Dummer, R. et al. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 19, 1315\u20131327 (2018).","journal-title":"Lancet Oncol."},{"key":"52694_CR12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/bjc.2013.721","volume":"110","author":"J-Y Douillard","year":"2013","unstructured":"Douillard, J.-Y. et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br. J. Cancer 110, 55\u201362 (2013).","journal-title":"Br. J. Cancer"},{"key":"52694_CR13","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1634\/theoncologist.2014-0089","volume":"19","author":"S Khozin","year":"2014","unstructured":"Khozin, S. et al. U.S. Food and Drug Administration approval summary: erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. Oncologist 19, 774\u2013779 (2014).","journal-title":"Oncologist"},{"key":"52694_CR14","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1158\/1078-0432.CCR-15-2266","volume":"22","author":"D Kazandjian","year":"2016","unstructured":"Kazandjian, D. et al. FDA approval of gefitinib for the treatment of patients with metastatic EGFR mutation\u2013positive non\u2013small cell lung cancer. Clin. Cancer Res. 22, 1307\u20131312 (2016).","journal-title":"Clin. Cancer Res."},{"key":"52694_CR15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1056\/NEJMoa1713137","volume":"378","author":"J-C 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":"52694_CR16","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/S1470-2045(15)00188-6","volume":"16","author":"C Le Tourneau","year":"2015","unstructured":"Le Tourneau, C. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 16, 1324\u20131334 (2015).","journal-title":"Lancet Oncol."},{"key":"52694_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1200\/PO.17.00002","volume":"2017","author":"A-M Tsimberidou","year":"2017","unstructured":"Tsimberidou, A.-M. et al. Initiative for molecular profiling and advanced cancer therapy (IMPACT): an MD Anderson Precision Medicine Study. JCO Precis. Oncol. 2017, 1\u201318 (2017).","journal-title":"JCO Precis. Oncol."},{"key":"52694_CR18","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1200\/PO.20.00372","volume":"5","author":"AP Chen","year":"2021","unstructured":"Chen, A. P. et al. Molecular profiling-based assignment of cancer therapy (NCI-MPACT): a randomized multicenter phase II trial. JCO Precis. Oncol. 5, 133\u2013144 (2021).","journal-title":"JCO Precis. Oncol."},{"key":"52694_CR19","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41591-019-0407-5","volume":"25","author":"JK Sicklick","year":"2019","unstructured":"Sicklick, J. K. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat. Med. 25, 744\u2013750 (2019).","journal-title":"Nat. Med."},{"key":"52694_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00969-w","volume":"13","author":"JK Sicklick","year":"2021","unstructured":"Sicklick, J. K. et al. Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naive study. Genome Med. 13, 155 (2021).","journal-title":"Genome Med."},{"key":"52694_CR21","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1158\/1078-0432.CCR-21-3752","volume":"28","author":"LR Hoes","year":"2022","unstructured":"Hoes, L. R. et al. Patients with rare cancers in the drug rediscovery protocol (DRUP) benefit from genomics-guided treatment. Clin. Cancer Res. 28, 1402\u20131411 (2022).","journal-title":"Clin. Cancer Res."},{"key":"52694_CR22","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41591-019-0424-4","volume":"25","author":"J Rodon","year":"2019","unstructured":"Rodon, J. et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat. Med. 25, 751\u2013758 (2019).","journal-title":"Nat. Med."},{"key":"52694_CR23","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1158\/2159-8290.CD-21-0126","volume":"11","author":"P Horak","year":"2021","unstructured":"Horak, P. et al. Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers. Cancer Discov. 11, 2780\u20132795 (2021).","journal-title":"Cancer Discov."},{"key":"52694_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-18613-3","volume":"11","author":"S Kato","year":"2020","unstructured":"Kato, S. et al. Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-one strategy. Nat. Commun. 11, 1\u20139 (2020).","journal-title":"Nat. Commun."},{"key":"52694_CR25","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ccell.2021.01.004","volume":"39","author":"A Irmisch","year":"2021","unstructured":"Irmisch, A. et al. The tumor profiler study: integrated, multi-omic, functional tumor profiling for clinical decision support. Cancer Cell 39, 288\u2013293 (2021).","journal-title":"Cancer Cell"},{"key":"52694_CR26","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1158\/2159-8290.CD-21-0538","volume":"12","author":"C Kornauth","year":"2022","unstructured":"Kornauth, C. et al. Functional precision medicine provides clinical benefit in advanced aggressive hematologic cancers and identifies exceptional responders. Cancer Discov. 12, 372\u2013387 (2022).","journal-title":"Cancer Discov."},{"key":"52694_CR27","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1158\/2159-8290.CD-21-0410","volume":"12","author":"D Malani","year":"2022","unstructured":"Malani, D. et al. Implementing a functional precision medicine tumor board for acute myeloid leukemia. Cancer Discov. 12, 388\u2013401 (2022).","journal-title":"Cancer Discov."},{"key":"52694_CR28","first-page":"28","volume":"19","author":"JW Tyner","year":"2018","unstructured":"Tyner, J. W. et al. Functional genomic landscape of acute myeloid leukaemia. Nature 19, 28 (2018).","journal-title":"Nature"},{"key":"52694_CR29","doi-asserted-by":"crossref","unstructured":"Davidson, B., Firat, P. & Michael, C. W. Serous effusions: etiology, diagnosis, prognosis and therapy. 115\u2013175 (Springer London, 2011).","DOI":"10.1007\/978-0-85729-697-9"},{"key":"52694_CR30","doi-asserted-by":"crossref","unstructured":"Davidson, B. Molecular testing on serous effusions. Diagn. Cytopathol. 49, 640\u2013646 (2020).","DOI":"10.1002\/dc.24392"},{"key":"52694_CR31","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nrc3820","volume":"14","author":"C Alix-Panabi\u00e8res","year":"2014","unstructured":"Alix-Panabi\u00e8res, C. & Pantel, K. Challenges in circulating tumour cell research. Nat. Rev. Cancer 14, 623\u2013631 (2014).","journal-title":"Nat. Rev. Cancer"},{"key":"52694_CR32","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/cncy.21522","volume":"123","author":"RH Shah","year":"2015","unstructured":"Shah, R. H. et al. Comprehensive mutation profiling by next-generation sequencing of effusion fluids from patients with high-grade serous ovarian carcinoma. Cancer Cytopathol. 123, 289\u2013297 (2015).","journal-title":"Cancer Cytopathol."},{"key":"52694_CR33","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/gcc.22509","volume":"57","author":"J Leichsenring","year":"2018","unstructured":"Leichsenring, J. et al. Targeted deep sequencing of effusion cytology samples is feasible, informs spatiotemporal tumor evolution, and has clinical and diagnostic utility. Genes Chromosomes Cancer 57, 70\u201379 (2018).","journal-title":"Genes Chromosomes Cancer"},{"key":"52694_CR34","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.21037\/jtd.2018.04.125","volume":"10","author":"L Liu","year":"2018","unstructured":"Liu, L. et al. Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens. J. Thorac. Dis. 10, 2631\u20132637 (2018).","journal-title":"J. Thorac. Dis."},{"key":"52694_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-709","volume":"14","author":"A Szulkin","year":"2014","unstructured":"Szulkin, A. et al. Characterization and drug sensitivity profiling of primary malignant mesothelioma cells from pleural effusions. BMC Cancer 14, 709 (2014).","journal-title":"BMC Cancer"},{"key":"52694_CR36","doi-asserted-by":"publisher","first-page":"25619","DOI":"10.18632\/oncotarget.4627","volume":"6","author":"JY Lee","year":"2015","unstructured":"Lee, J. Y. et al. Patient-derived cell models as preclinical tools for genome-directed targeted therapy. Oncotarget 6, 25619\u201325630 (2015).","journal-title":"Oncotarget"},{"key":"52694_CR37","doi-asserted-by":"publisher","first-page":"82885","DOI":"10.18632\/oncotarget.20889","volume":"8","author":"CO Hillerdal","year":"2017","unstructured":"Hillerdal, C. O. et al. Ex vivo evaluation of tumor cell specific drug responses in malignant pleural effusions. Oncotarget 8, 82885\u201382896 (2017).","journal-title":"Oncotarget"},{"key":"52694_CR38","doi-asserted-by":"publisher","first-page":"6981","DOI":"10.21873\/anticanres.13920","volume":"39","author":"C Vinayanuwattikun","year":"2019","unstructured":"Vinayanuwattikun, C. et al. Feasibility technique of low-passage in vitro drug sensitivity testing of malignant pleural effusion from advanced-stage non-small cell lung cancer for prediction of clinical outcome. Anticancer Res. 39, 6981\u20136988 (2019).","journal-title":"Anticancer Res."},{"key":"52694_CR39","doi-asserted-by":"crossref","unstructured":"Papp, E. et al. Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas. BMJ Open Respir. Res. 7, e000505 (2020).","DOI":"10.1136\/bmjresp-2019-000505"},{"key":"52694_CR40","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02613-4","volume":"18","author":"R Sheta","year":"2020","unstructured":"Sheta, R. et al. Development of a 3D functional assay and identification of biomarkers, predictive for response of high-grade serous ovarian cancer (HGSOC) patients to poly-ADP ribose polymerase inhibitors (PARPis): targeted therapy. J. Transl. Med. 18, 439 (2020).","journal-title":"J. Transl. Med."},{"key":"52694_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10318-5","volume":"12","author":"H-Y Seo","year":"2022","unstructured":"Seo, H.-Y. et al. Culture and multiomic analysis of lung cancer patient-derived pleural effusions revealed distinct druggable molecular types. Sci. Rep. 12, 6345 (2022).","journal-title":"Sci. Rep."},{"key":"52694_CR42","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1007\/s00432-019-03004-z","volume":"145","author":"J Li","year":"2019","unstructured":"Li, J. et al. Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening. J. Cancer Res. Clin. Oncol. 145, 2637\u20132647 (2019).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"52694_CR43","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.ygyno.2020.03.026","volume":"157","author":"H Chen","year":"2020","unstructured":"Chen, H. et al. Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma. Gynecol. Oncol. 157, 783\u2013792 (2020).","journal-title":"Gynecol. Oncol."},{"key":"52694_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100911","volume":"4","author":"H-M 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":"52694_CR45","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1158\/2643-3230.BCD-21-0219","volume":"3","author":"T Heinemann","year":"2022","unstructured":"Heinemann, T. et al. Deep morphology learning enhances ex vivo drug profiling-based precision medicine. Blood Cancer Discov. 3, 502\u2013515 (2022).","journal-title":"Blood Cancer Discov."},{"key":"52694_CR46","doi-asserted-by":"publisher","first-page":"e595","DOI":"10.1016\/S2352-3026(17)30208-9","volume":"4","author":"B Snijder","year":"2017","unstructured":"Snijder, B. et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 4, e595\u2013e606 (2017).","journal-title":"Lancet Haematol."},{"key":"52694_CR47","doi-asserted-by":"crossref","unstructured":"Kropivsek, K. et al. Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma. Nat. Cancer 4, 734\u2013753 (2023).","DOI":"10.1038\/s43018-023-00544-9"},{"key":"52694_CR48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-020-02015-1","volume":"21","author":"R Argelaguet","year":"2020","unstructured":"Argelaguet, R. et al. MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data. Genome Biol. 21, 1\u201317 (2020).","journal-title":"Genome Biol."},{"key":"52694_CR49","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20178124","volume":"14","author":"R Argelaguet","year":"2018","unstructured":"Argelaguet, R. et al. Multi-omics factor analysis\u2014a framework for unsupervised integration of multi-omics data sets. Mol. Syst. Biol. 14, e8124 (2018).","journal-title":"Mol. Syst. Biol."},{"key":"52694_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06500-x","volume":"9","author":"C Ye","year":"2018","unstructured":"Ye, C. et al. DRUG-seq for miniaturized high-throughput transcriptome profiling in drug discovery. Nat. Commun. 9, 4307 (2018).","journal-title":"Nat. Commun."},{"key":"52694_CR51","doi-asserted-by":"publisher","first-page":"D684","DOI":"10.1093\/nar\/gkm795","volume":"36","author":"M Kuhn","year":"2008","unstructured":"Kuhn, M., von Mering, C., Campillos, M., Jensen, L. J. & Bork, P. STITCH: interaction networks of chemicals and proteins. Nucleic Acids Res. 36, D684 (2008).","journal-title":"Nucleic Acids Res."},{"key":"52694_CR52","doi-asserted-by":"publisher","first-page":"D380","DOI":"10.1093\/nar\/gkv1277","volume":"44","author":"D Szklarczyk","year":"2016","unstructured":"Szklarczyk, D. et al. STITCH 5: augmenting protein\u2013chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 44, D380 (2016).","journal-title":"Nucleic Acids Res."},{"key":"52694_CR53","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","volume":"49","author":"D Szklarczyk","year":"2021","unstructured":"Szklarczyk, D. et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets. Nucleic Acids Res. 49, D605\u2013D612 (2021).","journal-title":"Nucleic Acids Res."},{"key":"52694_CR54","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nrc1317","volume":"4","author":"MA Jordan","year":"2004","unstructured":"Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4, 253\u2013265 (2004).","journal-title":"Nat. Rev. Cancer"},{"key":"52694_CR55","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12890-021-01803-0","volume":"22","author":"P Paliogiannis","year":"2022","unstructured":"Paliogiannis, P. et al. Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study. BMC Pulm. Med. 22, 32 (2022).","journal-title":"BMC Pulm. Med."},{"key":"52694_CR56","doi-asserted-by":"publisher","first-page":"2801","DOI":"10.3390\/cancers12102801","volume":"12","author":"I Proietti","year":"2020","unstructured":"Proietti, I. et al. Mechanisms of acquired BRAF inhibitor resistance in melanoma: a systematic review. Cancers 12, 2801 (2020).","journal-title":"Cancers"},{"key":"52694_CR57","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41388-021-02076-x","volume":"41","author":"K Ingram","year":"2021","unstructured":"Ingram, K. et al. NKX2-1 controls lung cancer progression by inducing DUSP6 to dampen ERK activity. Oncogene 41, 293\u2013300 (2021).","journal-title":"Oncogene"},{"key":"52694_CR58","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.3390\/ijms20082036","volume":"20","author":"V Moncho-Amor","year":"2019","unstructured":"Moncho-Amor, V. et al. Role of Dusp6 phosphatase as a tumor suppressor in non-small cell lung cancer. Int. J. Mol. Sci. 20, 2036 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"52694_CR59","doi-asserted-by":"publisher","first-page":"14","DOI":"10.20892\/j.issn.2095-3941.2017.0107","volume":"15","author":"MK Ahmad","year":"2018","unstructured":"Ahmad, M. K., Abdollah, N. A., Shafie, N. H., Yusof, N. M. & Razak, S. R. A. Dual-specificity phosphatase 6 (DUSP6): a review of its molecular characteristics and clinical relevance in cancer. Cancer Biol. Med. 15, 14 (2018).","journal-title":"Cancer Biol. Med."},{"key":"52694_CR60","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1913662","volume":"382","author":"SS Ramalingam","year":"2020","unstructured":"Ramalingam, S. S. et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N. Engl. J. Med. 382, 41\u201350 (2020).","journal-title":"N. Engl. J. Med."},{"key":"52694_CR61","first-page":"962","volume":"7","author":"M Friese-Hamim","year":"2017","unstructured":"Friese-Hamim, M., Bladt, F., Locatelli, G., Stammberger, U. & Blaukat, A. The selective c-Met inhibitor tepotinib can overcome epidermal growth factor receptor inhibitor resistance mediated by aberrant c-Met activation in NSCLC models. Am. J. Cancer Res. 7, 962\u2013972 (2017).","journal-title":"Am. J. Cancer Res."},{"key":"52694_CR62","doi-asserted-by":"publisher","first-page":"3101","DOI":"10.1200\/JCO.2018.77.7326","volume":"36","author":"Y-L Wu","year":"2018","unstructured":"Wu, Y.-L. et al. Phase Ib\/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J. Clin. Oncol. 36, 3101\u20133109 (2018).","journal-title":"J. Clin. Oncol."},{"key":"52694_CR63","first-page":"100162","volume":"2","author":"O Gautschi","year":"2021","unstructured":"Gautschi, O. & Diebold, J. Intracranial activity of osimertinib plus capmatinib in a patient with EGFR and MET-driven lung cancer: case report. JTO Clin. Res. Rep. 2, 100162 (2021).","journal-title":"JTO Clin. Res. Rep."},{"key":"52694_CR64","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1016\/j.jtho.2019.07.027","volume":"15","author":"O Gautschi","year":"2020","unstructured":"Gautschi, O., Menon, R., Bertrand, M., Murer, C. & Diebold, J. Capmatinib and osimertinib combination therapy for EGFR-mutant lung adenocarcinoma. J. Thorac. Oncol. 15, e13\u2013e15 (2020).","journal-title":"J. Thorac. Oncol."},{"key":"52694_CR65","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1016\/S2213-2600(20)30154-5","volume":"8","author":"Y-L Wu","year":"2020","unstructured":"Wu, Y.-L. et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b\/2, multicentre, randomised trial. Lancet Respir. Med. 8, 1132\u20131143 (2020).","journal-title":"Lancet Respir. Med."},{"key":"52694_CR66","first-page":"TPS9153","volume":"40","author":"Y-L Wu","year":"2022","unstructured":"Wu, Y.-L. et al. Capmatinib plus osimertinib versus platinum-pemetrexed doublet chemotherapy as second-line therapy in patients with stage IIIb\/IIIc or IV EGFR-mutant, T790M-negative NSCLC harboring MET amplification. J. Clin. Orthod. 40, TPS9153\u2013TPS9153 (2022).","journal-title":"J. Clin. Orthod."},{"key":"52694_CR67","doi-asserted-by":"publisher","first-page":"102173","DOI":"10.1016\/j.ctrv.2021.102173","volume":"95","author":"Y-L Wu","year":"2021","unstructured":"Wu, Y.-L., Smit, E. F. & Bauer, T. M. Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies. Cancer Treat. Rev. 95, 102173 (2021).","journal-title":"Cancer Treat. Rev."},{"key":"52694_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-27026-9","volume":"12","author":"Z-Y Huang","year":"2021","unstructured":"Huang, Z.-Y. et al. Single-cell analysis of diverse immune phenotypes in malignant pleural effusion. Nat. Commun. 12, 1\u201312 (2021).","journal-title":"Nat. Commun."},{"key":"52694_CR69","first-page":"1","volume":"14","author":"X-Z Huang","year":"2023","unstructured":"Huang, X.-Z. et al. Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis. Nat. Commun. 14, 1\u201322 (2023).","journal-title":"Nat. Commun."},{"key":"52694_CR70","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00991-4","volume":"20","author":"RF Carvalho","year":"2022","unstructured":"Carvalho, R. F. et al. Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer. Cell Commun. Signal. 20, 176 (2022).","journal-title":"Cell Commun. Signal."},{"key":"52694_CR71","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1038\/s41467-020-16164-1","volume":"11","author":"N Kim","year":"2020","unstructured":"Kim, N. et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat. Commun. 11, 2285\u20132285 (2020).","journal-title":"Nat. Commun."},{"key":"52694_CR72","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1038\/s12276-020-00538-y","volume":"52","author":"HH Eum","year":"2020","unstructured":"Eum, H. H. et al. Tumor-promoting macrophages prevail in malignant ascites of advanced gastric cancer. Exp. Mol. Med. 52, 1976\u20131988 (2020).","journal-title":"Exp. Mol. Med."},{"key":"52694_CR73","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105358","volume":"25","author":"H-O Jeong","year":"2022","unstructured":"Jeong, H.-O. et al. Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma. iScience 25, 105358 (2022).","journal-title":"iScience"},{"key":"52694_CR74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1091\/mbc.e10-04-0335","volume":"23","author":"TJ Mitchison","year":"2012","unstructured":"Mitchison, T. J. The proliferation rate paradox in antimitotic chemotherapy. Mol. Biol. Cell 23, 1\u20136 (2012).","journal-title":"Mol. Biol. Cell"},{"key":"52694_CR75","doi-asserted-by":"publisher","unstructured":"Maynard, A. et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing, https:\/\/doi.org\/10.1016\/j.cell.2020.07.017. (2020).","DOI":"10.1016\/j.cell.2020.07.017"},{"key":"52694_CR76","first-page":"1437","volume":"171","author":"A Subramanian","year":"2017","unstructured":"Subramanian, A. et al. A next generation connectivity map: L1000 platform and the first 1,000,000. Profiles Cell 171, 1437\u20131452.e17 (2017).","journal-title":"Profiles Cell"},{"key":"52694_CR77","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1021\/acschembio.1c00920","volume":"17","author":"J Li","year":"2022","unstructured":"Li, J. et al. DRUG-seq provides unbiased biological activity readouts for neuroscience drug discovery. ACS Chem. Biol. 17, 1401\u20131414 (2022).","journal-title":"ACS Chem. Biol."},{"key":"52694_CR78","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.annonc.2020.03.293","volume":"31","author":"M Schuler","year":"2020","unstructured":"Schuler, M. et al. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann. Oncol. 31, 789\u2013797 (2020).","journal-title":"Ann. Oncol."},{"key":"52694_CR79","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","volume":"30","author":"Z Gu","year":"2014","unstructured":"Gu, Z., Gu, L., Eils, R., Schlesner, M. & Brors, B. circlize Implements and enhances circular visualization in. R. Bioinform. 30, 2811\u20132812 (2014).","journal-title":"R. Bioinform."},{"key":"52694_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-10-r100","volume":"7","author":"AE Carpenter","year":"2006","unstructured":"Carpenter, A. E. et al. CellProfiler: Image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 7, R100 (2006).","journal-title":"Genome Biol."},{"key":"52694_CR81","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nchembio.2360","volume":"13","author":"GI Vladimer","year":"2017","unstructured":"Vladimer, G. I. et al. Global survey of the immunomodulatory potential of common drugs. Nat. Chem. Biol. 13, 681\u2013690 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"52694_CR82","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41586-022-05028-x","volume":"608","author":"J Shilts","year":"2022","unstructured":"Shilts, J. et al. A physical wiring diagram for the human immune system. Nature 608, 397\u2013404 (2022).","journal-title":"Nature"},{"key":"52694_CR83","doi-asserted-by":"publisher","unstructured":"Wegmann, R. Molecular and functional landscape of malignant serous effusions for precision oncology: DRUG-seq toolbox. https:\/\/doi.org\/10.5281\/zenodo.13310707 (2024).","DOI":"10.5281\/zenodo.13310707"},{"key":"52694_CR84","first-page":"2122","volume":"5","author":"ATL Lun","year":"2016","unstructured":"Lun, A. T. L., McCarthy, D. J. & Marioni, J. C. A step-by-step workflow for low-level analysis of single-cell RNA-seq data with bioconductor. F1000Res 5, 2122 (2016).","journal-title":"F1000Res"},{"key":"52694_CR85","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"52694_CR86","first-page":"2579","volume":"9","author":"L van der Maaten","year":"2008","unstructured":"van der Maaten, L. & Hinton, G. E. Visualizing high-dimensional data using t-SNE. J. Mach. Learn. Res. 9, 2579\u20132605 (2008).","journal-title":"J. Mach. Learn. Res."},{"key":"52694_CR87","first-page":"3221","volume":"15","author":"L van der Maaten","year":"2014","unstructured":"van der Maaten, L. Accelerating t-SNE using tree-based algorithms. J. Mach. Learn. Res. 15, 3221\u20133245 (2014).","journal-title":"J. Mach. Learn. Res."},{"key":"52694_CR88","doi-asserted-by":"crossref","unstructured":"Krijthe, J. H. & Van der Maaten, L. Rtsne: T-distributed stochastic neighbor embedding using Barnes-Hut implementation. https:\/\/github.com\/jkrijthe\/Rtsne (2015).","DOI":"10.32614\/CRAN.package.Rtsne"},{"key":"52694_CR89","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"52694_CR90","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1093\/nar\/gks042","volume":"40","author":"DJ McCarthy","year":"2012","unstructured":"McCarthy, D. J., Chen, Y. & Smyth, G. K. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res. 40, 4288\u20134297 (2012).","journal-title":"Nucleic Acids Res."},{"key":"52694_CR91","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2435-4","volume":"19","author":"M Foroutan","year":"2018","unstructured":"Foroutan, M. et al. Single sample scoring of molecular phenotypes. BMC Bioinform. 19, 404 (2018).","journal-title":"BMC Bioinform."},{"key":"52694_CR92","doi-asserted-by":"crossref","unstructured":"Love, M. I., Anders, S. & Huber, W. Differential analysis of count data - DESeq2 Package. https:\/\/www.marcjoiret.be\/pdfs\/DESeq2package.pdf15, 550 (2014).","DOI":"10.1186\/s13059-014-0550-8"},{"key":"52694_CR93","unstructured":"Csardi, G. & Nepusz, T. The igraph software package for complex network research. InterJournal vol. Complex Systems 1695. https:\/\/igraph.org (2006)."},{"key":"52694_CR94","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/nbt.2696","volume":"31","author":"GM Frampton","year":"2013","unstructured":"Frampton, G. M. et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat. Biotechnol. 31, 1023\u20131031 (2013).","journal-title":"Nat. Biotechnol."},{"key":"52694_CR95","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.1182\/blood-2015-08-664649","volume":"127","author":"J He","year":"2016","unstructured":"He, J. et al. Integrated genomic DNA\/RNA profiling of hematologic malignancies in the clinical setting. Blood 127, 3004\u20133014 (2016).","journal-title":"Blood"},{"key":"52694_CR96","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2","volume":"9","author":"ZR Chalmers","year":"2017","unstructured":"Chalmers, Z. R. et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 9, 34 (2017).","journal-title":"Genome Med."},{"key":"52694_CR97","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez, N. S. et al. Identification of actionable genomic alterations using circulating cell-free DNA. JCO Precis. Oncol. 3, PO.19.00017 (2019).","DOI":"10.1200\/PO.19.00017"},{"key":"52694_CR98","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847\u20132849 (2016).","journal-title":"Bioinformatics"},{"key":"52694_CR99","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/nmeth.1584","volume":"8","author":"L Reiter","year":"2011","unstructured":"Reiter, L. et al. mProphet: automated data processing and statistical validation for large-scale SRM experiments. Nat. Methods 8, 430\u2013435 (2011).","journal-title":"Nat. Methods"},{"key":"52694_CR100","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.1021\/pr070230d","volume":"6","author":"B Zhang","year":"2007","unstructured":"Zhang, B., Chambers, M. C. & Tabb, D. L. Proteomic parsimony through bipartite graph analysis improves accuracy and transparency. J. Proteome Res. 6, 3549\u20133557 (2007).","journal-title":"J. Proteome Res."},{"key":"52694_CR101","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-10-r80","volume":"5","author":"RC Gentleman","year":"2004","unstructured":"Gentleman, R. C. et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80 (2004).","journal-title":"Genome Biol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52694-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52694-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52694-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T17:01:43Z","timestamp":1727888503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-52694-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,2]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["52694"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-52694-8","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,2]]},"assertion":[{"value":"14 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.S. was a scientific co-founder of Allcyte, which has been acquired by Exscientia. B.S. is a shareholder of Exscientia and a co-inventor on US patent application 15\/514,045 relevant to the study. C.B. reports consulting or advisory role for AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer-Ingelheim, Merck KGaA, Sanofi; research funding from Bayer; and travel, accommodation, and expenses from AstraZeneca, Takeda, Amgen. All of those are outside the presented work. H.M. is on advisory boards for Astra Zeneca, Stemline Therapeutics, Bayer, Amgen, Astella, MSD, Roche, and Merck. M.Z. receives research funds from Roche. P.P. is a scientific advisor for the company Biognosys AG (Zurich, Switzerland). All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8544"}}