Identification of KLK10 as a therapeutic target to reverse trastuzumab resistance in breast cancer.
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.
Department of Medical Oncology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Zhuo
Z
Wang
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Beihong
B
Ruan
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.|Department of Clinical Medicine, Ningbo University, Ningbo, China.
Yi
Y
Jin
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Yulong
Y
Zhang
Department of Medical Oncology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Jiaqiu
J
Li
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Liyuan
L
Zhu
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Wenxia
W
Xu
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Lifeng
L
Feng
Laboratory of Cancer Biology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Hongchuan
H
Jin
Department of Medical Oncology, Key lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.
Xian
X
Wang
D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019295:Computational Biology; D030541:Databases, Genetic; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D000068878:Trastuzumab / Q000627:therapeutic use*
D000074322:Antineoplastic Agents, Immunological; D007610:Kallikreins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C100936:KLK10 protein, human
HER2; KLK10; breast cancer; trastuzumab resistance