ArticleMolecular & cellular proteomics : MCP2026
Clone-By-Clone Therapy Guidance in Luminal Breast Cancer Via Spatial Proteomics and Patient-Derived Tumoroid.
Article in Molecular & cellular proteomics : MCP, 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
Breast cancer (BC) remains the leading cause of cancer-related death among women worldwide, with 2.26 million new cases and ∼685,000 deaths reported in 2020 (Globocan 2020). A major challenge in treating BC, particularly luminal subtypes, is the pronounced molecular heterogeneity both between patients and within individual tumors. This intratumoral diversity underlies many cases of therapy resistance and relapse. Here, we present a theranostic approach that integrates spatial proteomics and patient-derived tumoroids (PDTs) to guide personalized treatment in luminal BC. Formalin-fixed, paraffin-embedded tumor tissues from three patients were analyzed by MALDI mass spectrometry imaging and spatially resolved microproteomics, mapping distinct clonal subpopulations and their protein expression profiles. Proteomic pathway analysis revealed subclone-specific vulnerabilities that are not apparent from standard histopathology. We exploited these insights to design alternative combination therapies tailored to each tumor's molecular makeup. The efficacy of proteomics-guided regimens was then evaluated in vitro using PDTs established from the same patients, in direct comparison to conventional chemotherapy. Proteomic-informed treatments demonstrated significantly enhanced antitumor activity in the PDT models, yielding lower IC
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