Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer
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Zhuo Wang1,*, Beihong Ruan2,*, Yi Jin2,3, Yulong Zhang2, Jiaqiu Li1, Liyuan Zhu2, Wenxia Xu2, Lifeng Feng2, Hongchuan Jin2, Xian Wang1
1Department of Medical Oncology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
2Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China
3Department of Clinical Medicine, Ningbo University, Ningbo, China
*These authors contributed equally to this work
Xian Wang, email: firstname.lastname@example.org
Keywords: trastuzumab resistance, KLK10, breast cancer, HER2
Received: September 06, 2016 Accepted: October 12, 2016 Published: November 04, 2016
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.
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