The Impact of Epithelial Stromal Interactions on Human Breast Tumor Heterogeneity
Technical Report,15 Sep 2013,14 Sep 2016
ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING MONTREAL (CANADA) MONTREAL Canada
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Heterogeneity plays a substantial role in the variability of patient response to treatment, especially in triple-negative TN breast cancer. A fuller understanding of the molecularly distinct TN subgroups linked to outcome is essential to promote the development of more personalized treatment strategies. The goal of this project was to identify, define and formally test critical pathways mediating tumor epithelial-stromal communication and codependency in TN breast cancer. Interestingly, we established that tumor heterogeneity in TN disease could be captured by stromal-specific subtypes - immune infiltration, androgen receptor signalinginvasive epithelia and desmoplastic stroma. These subtypes were associated with distant metastasis free survival, suggesting that outcome in TN breast cancer may be stromal-dependent or even stromal driven. Our project has provided the first integrated in-depth analysis of the contribution of tumor stromal processes to TN disease heterogeneity, and has positioned the tumor microenvironment for therapeutic intervention.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research