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Trastuzumab, the first antibody widely used in anti-HER2 targeted therapy, dramatically improved the overall outcome of HER2 positive breast cancer patients. However, trastuzumab resistance emerged as a major problem in its clinical application. In order to explore mechanisms underlying trastuzumab resistance, we performed RNA-Seq to analyze the gene expression variation in trastuzumab resistant breast cancer cell line. The sequencing result was then combined with the relevant data in TCGA database to conduct a co-expression analysis. We found a series of differentially expressed genes with potential contributions to trastuzumab resistance. Among them, KLK10 was verified to be a potential therapeutic target for reversing trastuzumab resistance. In summary, this study provides a new clue to screen molecular targets and predictive biomarkers for trastuzumab resistance.

Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer