Fig. 10: Targeting c-Myc or cPLA2α overcomes HER2 antibody resistance in mice.

a Growth curve of HR6 tumors in mice treated with vehicle, trastuzumab (Tras.), MYCi361 (MYCi), or trastuzumab+MYCi361 (n = 5). b, c Representative Ki67 IHC image (b) and quantification (c) in tumors (n = 5). d, e Representative CC3 IHC image (d) and quantification (e) in tumors (n = 5). f Growth curve of HR6 tumors in mice treated with vehicle, trastuzumab, CDIBA, or trastuzumab+CDIBA (n = 5). g, h Representative CC3 IHC image (g) and quantification (h) in tumors (n = 5). i Growth curve of BCM-4169 tumors in mice treated with vehicle, trastuzumab, MYCi361, or trastuzumab+MYCi361 (n = 4). j, k Representative CC3 IHC image (j) and quantification (k) in tumors (n = 4). l Growth curve of BCM-4169 tumors in mice treated with vehicle, trastuzumab, CDIBA, or trastuzumab+CDIBA (n = 5). m, n Representative CC3 IHC image (m) and quantification (n) in tumors (n = 5). o Growth curve of BCM-4169 tumors in mice treated with vehicle, trastuzumab+pertuzumab (Pert.), trastuzumab+pertuzumab+MYCi361 or CDIBA (n = 5). p, q Representative CC3 IHC image (p) and quantification (q) in tumors (n = 5). r Kaplan–Meier survival curve of BCM-4169 tumor-bearing mice treated with vehicle, trastuzumab+pertuzumab, trastuzumab+pertuzumab+MYCi361 or CDIBA. s A working model of the ZMYND8-c-Myc-cPLA2α-IL-27 axis-induced anti-HER2 therapy resistance in HER2+ breast cancer. Data from biological replicates represent mean ± SEM. P-value was determined by one-way ANOVA with Dunnett’s test (q) or Tukey’s test (e, h, k, and n), two-way ANOVA with Tukey’s test (a, f, i, l, and o), or log-rank test (r). Scale bar, 100 μm. Source data are provided as a Source Data file.