Fig. 7: cPLA2α drives HER2 antibody resistance in HER2+ breast cancer.

a–c Clonogenic growth of parental, cPLA2α KO1, and cPLA2α KO2 HR6 cells treated with vehicle or trastuzumab (Tras.) for 6 days. Immunoblot analysis (a, n = 3), representative colony images (b), and quantification (c, n = 3). d, e Clonogenic growth of parental, cPLA2α KO1, and cPLA2α KO2 HR6 cells treated with vehicle, trastuzumab, pertuzumab (Pert.), or trastuzumab+pertuzumab for 6 days. Representative colony images (d) and quantification (e, n = 3). f–h Clonogenic growth of parental, cPLA2α KO1, cPLA2α KO1 + cPLA2α-WT and cPLA2α KO1 + S505A mutant HR6 cells treated with vehicle or trastuzumab for 6 days. Immunoblot analysis (f, n = 3), representative colony images (g), and quantification (h, n = 3). i, j Clonogenic growth of HR6 cells treated with vehicle, trastuzumab, CDIBA, or trastuzumab+CDIBA for 6 days. Representative colony images (i) and quantification (j, n = 2). k–n Growth of tumor organoids treated with vehicle, trastuzumab, CDIBA, or trastuzumab+CDIBA for 9 days. Representative organoid images (k, m) and organoid viability quantification (l, n, n = 3). o–r Growth of tumor organoids treated with vehicle, trastuzumab, CDIBA, trastuzumab+pertuzumab, trastuzumab+CDIBA, or trastuzumab+pertuzumab+CDIBA for 9 days. Representative organoid images (o, q) and organoid viability quantification (p, r, n = 3). s–u Growth of parental, cPLA2α KO1 and cPLA2α KO2 HR6 tumors in mice treated with vehicle or trastuzumab. Tumor growth curve (s), tumor weight (t), and the percentage of tumor inhibition (u, n = 5). Data from biological replicates represent mean ± SEM. P-value was determined by one-way ANOVA with Tukey’s test (p and r) or Dunnett’s test (u), or two-way ANOVA with Tukey’s test (c, e, h, l, n, s, and t). Scale bar, 200 μm. Source data are provided as a Source Data file.