A Biophysical Stromal Basis for Radiation Sensitivity in Ductal Carcinoma in situ

We hypothesize that high tensile forces of activated stroma play a critical role in the survival and proliferation of cancerous epithelial cells through direct involvement of the YAP-TAZ and PI3-k pathways, and that disengaging pro-survival mechanosignaling emanating from the activated stroma is a promising approach to enhancing therapeutic efficacy. Our goals are to determine if tensile forces specifically regulate ionizing radiation (IR) therapy resistance by testing 1) whether the YAP-TAZ and PI3-k pathways are acting independently in IR-mediated cell death and proliferation; and 2) whether integrin mechanosignaling modifies this regulation. In addition, we have the unique opportunity to investigate whether stromal biophysical and morphological features are associated YAP-TAZ signaling and disease progression in clinical DCIS.

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