In this section, we set out to evaluate the effects of TRAF4 inhibition on activity of the HER2 downstream AKT/mTOR signaling pathway in HER2+ PDX BJ11 derived organoids and HER2+ breast cancer cells, including the Trastuzumab-resistant parental HCC1954 cells, the Trastuzumab-sensitive parental BT474 cells, and secondary Trastuzumab-resistant BT474 cells (sensitivity to Trastuzumab of these cells is shown in Fig. 3C and Supplementary Fig. S8 [11, 35–37]). This evidence concerns the gene ERBB2 and breast carcinoma.