{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:17Z","timestamp":1789707857307,"version":"4.0.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate, has demonstrated clinical activity in HER2-positive and HER2-low advanced breast cancer. However, treatment outcomes remain heterogeneous, and circulating molecular correlates of treatment and prognosis are incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-nine patients receiving T-DXd were included in the clinical cohort, of whom 16 provided paired pre- and post-two-cycle plasma for multi-omics profiling. Proteomics used 4D-DIA LC-MS\/MS; metabolomics used UHPLC-high-resolution MS in positive\/negative modes. Treatment-associated features were identified by paired statistics, fold change, and multivariate criteria, followed by enrichment, correlation, joint pathway mapping, and exploratory PFS-oriented Cox\/LASSO-Cox analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomics identified 4,444 proteins; 508 were differentially expressed (136 up, 372 down), enriched in translation\/ribosome, complement\/coagulation, acute-phase, cytoskeletal\/adhesion, and lipid transport pathways. Metabolomics detected 3,596 features; 70 were differential (43 up, 27 down), enriched in amino acid, tryptophan, nucleotide\/energy, and lipid metabolism. Cross-omics analysis revealed structured correlations and joint purine metabolism mapping. Exploratory baseline analyses selected six protein and four metabolite prognostic biomarkers for PFS visualization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Paired plasma multi-omics revealed T-DXd-associated proteomic and metabolic remodeling. The molecular patterns and PFS-associated biomarkers are hypothesis-generating and require validation in larger independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1973097","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:37:28Z","timestamp":1789706248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma multi-omics reveals molecular remodeling and prognostic biomarkers in advanced breast cancer treated with trastuzumab deruxtecan"],"prefix":"10.3389","volume":"16","author":[{"given":"Die","family":"Sang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Yang","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of VIP Medical Services, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Liu","sequence":"additional","affiliation":[{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]},{"name":"Department of VIP Medical Services, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fudan University Affiliated Cancer Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of VIP Medical Services, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical 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