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

// Zhuo Wang 1, * , Beihong Ruan 2, * , Yi Jin 2, 3 , Yulong Zhang 2 , Jiaqiu Li 1 , Liyuan Zhu 2 , Wenxia Xu 2 , Lifeng Feng 2 , Hongchuan Jin 2 , Xian Wang 1 1 Department of Medical Oncology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China 2 Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China 3 Department of Clinical Medicine, Ningbo University, Ningbo, China * These authors contributed equally to this work Correspondence to: Xian Wang, email: wangxzju@163.com Keywords: trastuzumab resistance, KLK10, breast cancer, HER2 Received: September 06, 2016 Accepted: October 12, 2016 Published: November 04, 2016 ABSTRACT 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.