ArticleFrontiers in oncology2026
Plasma multi-omics reveals molecular remodeling and prognostic biomarkers in advanced breast cancer treated with trastuzumab deruxtecan.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
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