Autopsy-based longitudinal multi-organ high-dimensional profiling reveals lineage plasticity in TRK-inhibitor-resistant secretory breast carcinoma
Secretory breast carcinoma (SBC) is typically indolent, yet mechanisms underlying aggressiveness and therapeutic resistance to tropomyosin receptor kinase inhibitors (TRKi) remain unclear. Autopsy-based longitudinal multi-organ high-dimensional profiling of metastatic TRKi-resistant SBC demonstrated histopathological heterogeneity, including secretory and squamous components, arising from a shared clonal origin. Integrated genomic and transcriptomic analyses revealed hierarchical transcriptional rewiring consistent with a lineage-plastic state, suggesting a potential link to tumor aggressiveness and therapeutic resistance.
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