Spatially Resolved Transcriptomics Identifies Tumor-Stroma-Immune Networks and Therapeutic Targets in Endocrine-Resistant Advanced Breast Cancer Treated with Everolimus+Letrozole: Insights from the MI
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- The MIRACLE trial showed that everolimus plus letrozole (E+L) improves progression-free survival in premenopausal patients with endocrine-resistant, HR-positive, HER2-negative advanced breast cancer.
- Spatial transcriptomics identified distinct gene interaction networks in patients with shorter (≤3 years) and longer (>3 years) overall survival (OS).
- In shorter OS patients, tumor-derived S100A9 and CALML5 were linked to mTORC1 activation, suggesting tasquinimod (S100A9 inhibitor) as a potential therapy.
- CALML5 and SLPI interaction across tumor and immune areas may maintain tumor integrity and reduce immune-mediated damage.
- Longer OS patients exhibited SERPINA1 (linked to ER activation) and FKBP5-SESN3 interaction (associated with AKT/mTORC1 inhibition) in tumor-rich regions.
- MMP11-COL16A1 interaction in stroma-rich regions suggests cancer-associated fibroblasts may contribute to better outcomes.
- Spatial gene expression analysis highlights the tumor microenvironment's role in prognosis and identifies new therapeutic targets for E+L-treated patients.