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bioRxiv · 10.64898/2026.04.06.716668

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.
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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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Muroyama, Y., Yanagaki, M., Tada, H., Ebata, A., Ito, T., Ono, K., Tominaga, J., Miyashita, M., Suzuki, T.. 2026-04-08. Autopsy-based longitudinal multi-organ high-dimensional profiling reveals lineage plasticity in TRK-inhibitor-resistant secretory breast carcinoma. https://doi.org/10.64898/2026.04.06.716668

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