Figure 7.

Signal transducer and activator of transcription 3 (STAT3) inhibition overcomes trastuzumab‐emtansine (T‐DM1) resistance in vivo. A, Leukemia inhibitory factor receptor (LIFR) expression was detected on immunohistochemistry. Scale bar, 50 μm. B, BT‐474 and BT‐474/KR xenograft tumors were lysed. C, BT‐474/KR xenograft tumors and an equal amount of BT‐474/KR cells were lysed. D, Mice bearing BT‐474/KR xenograft tumors were treated with vehicle or napabucasin. Tumors were isolated and lysed. B‐D, Phosphorylated (activated) STAT3 (pSTAT3) was measured on western blotting. E, Nude mice bearing BT‐474/KR xenograft tumors were treated with T‐DM1, napabucasin, or a combination of T‐DM1 and napabucasin for 17 days. Tumor volume was measured on the indicated days. Error bars represent mean ± SD. n = 8. *P < .05, **P < .01. F, Proposed model of T‐DM1 resistance in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer