STAT3 and cancer: To probe the molecular alterations underlying trastuzumab resistance, we screened the status of alternative RTKs and their downstream signaling pathways previously implicated in trastuzumab resistance.[12-15] As shown in Fig. 1C, a significant increase in STAT3 phosphorylation (at Tyr705) was noted in both resistant cancer cells compared to their parental cells, which was also evident in tumor xenografts presenting an increased staining of phosphorylated STAT3 (Supplementary Fig. 1).