Fig. 7

Model of mechanism of tumor recurrence after BGJ398 treatment. Before the treatment with the FGFR inhibitor, BGJ398, Wnt1/iR1 tumor cells are surrounded by α-SMA⁺ myoepithelial cells and stroma, which is comprised of stromal fibroblasts, MDSCs, blood vessels and collagen. Upon BGJ398 treatment, the majority of the tumor cells die, leaving a nonpalpable mass of tumor cells with remodeled stroma, including thickened myoepithelial cell layers, increased collagen, and upregulation of tenascin-C. Vasculature and MDSCs are eliminated after BGJ398 treatment. Over time, EGFR signaling is upregulated, accompanied by remodeled stroma and tumor recurrence. The stroma in the recurrent tumors maintains elevated tenascin-C and increased collagen expression. However, the recurrent tumors have a disrupted myoepithelial cell layer and increased MDSC infiltration indicating that they may be more invasive as compared to the primary tumors. iR1 Inducible fibroblast growth factor receptor 1, MDSC Myeloid-derived tumor suppressor cell, p-EGFR Phosphorylated epidermal growth factor receptor