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Autopsy-based longitudinal multi-organ high-dimensional profiling reveals lineage plasticity in TRK-inhibitor-resistant secretory breast carcinoma

Muroyama, Y.; Yanagaki, M.; Tada, H.; Ebata, A.; Ito, T.; Ono, K.; Tominaga, J.; Miyashita, M.; Suzuki, T.

2026-04-08 pathology
10.64898/2026.04.06.716668 bioRxiv
Show abstract

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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