In conclusion, our work proposes a possible mechanism of trastuzumab resistance fostered by a STAT3-centered positive feedback loop comprising of FN/EGF/IL-6 upstream mediators and MUC1/4 downstream executioners in HER2-positive breast and gastric cancer, providing a rationale for applying STAT3 inhibitors to overcome trastuzumab resistance (Fig. 7B). The gene discussed is EGF; the disease is gastric cancer.