Literature DB >> 24492292

The ErbB2-targeting antibody trastuzumab and the small-molecule SRC inhibitor saracatinib synergistically inhibit ErbB2-overexpressing gastric cancer.

Siqi Han1, Yanchun Meng2, Qing Tong3, Guangchao Li4, Xunmin Zhang3, Yalin Chen3, Shi Hu3, Lei Zheng3, Wenlong Tan5, Hui Li6, Yang Chen6, Ge Zhang3, Bohua Li7, Yajun Guo8.   

Abstract

The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in ErbB2-overexpressing breast and gastric cancer, but resistance to the drug is common. Here, we investigated the antitumor activity of the combination of trastuzumab and the SRC inhibitor saracatinib in ErbB2-overexpressing trastuzumab-resistant gastric cancer. The ErbB2-overexpressing human gastric cancer cell line NCI-N87 was treated with trastuzumab to obtain the trastuzumab-resistant cell line NCI-N87R. The NCI-N87R cell line showed a marked increase in SRC activity and ErbB signaling compared with the NCI-N87 cell line. Our data demonstrated that trastuzumab plus saracatinib was much more potent than either agent alone in reducing the phosphorylation of ErbB3 and AKT in both NCI-N87 and NCI-N87R gastric cancer cell lines. Trastuzumab and saracatinib synergistically inhibited the in vitro growth of NCI-N87 and NCI-N87R cell lines. Further data showed that combination therapy of trastuzumab with saracatinib resulted in a significant benefit over either agent alone in both NCI-N87 and NCI-N87R xenograft models, suggesting its potential use for treating ErbB2-overexpressing gastric cancer.

Entities:  

Keywords:  ErbB2; SRC; gastric cancer; saracatinib; trastuzumab

Mesh：

Substances：

Year:  2013        PMID： 24492292      PMCID： PMC3984329          DOI： 10.4161/mabs.27443

Source DB:  PubMed          Journal:  MAbs        ISSN： 1942-0862            Impact factor:   5.857


  19 in total

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  16 in total

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Authors:  Eduardo Sanabria-Figueroa; Siobhan M Donnelly; Kevin C Foy; Meghan C Buss; Robert C Castellino; Elisavet Paplomata; Latonia Taliaferro-Smith; Pravin T P Kaumaya; Rita Nahta
Journal:  Mol Pharmacol       Date:  2014-11-12       Impact factor: 4.436

2.  Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop.

Authors:  Zhengyan Yang; Liang Guo; Dan Liu; Limin Sun; Hongyu Chen; Que Deng; Yanjun Liu; Ming Yu; Yuanfang Ma; Ning Guo; Ming Shi
Journal:  Oncotarget       Date:  2015-03-10

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4.  Feedback activation of STAT3 mediates trastuzumab resistance via upregulation of MUC1 and MUC4 expression.

Authors:  Guangchao Li; Likun Zhao; Wei Li; Kexing Fan; Weizhu Qian; Sheng Hou; Hao Wang; Jianxin Dai; Huafeng Wei; Yajun Guo
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Authors:  Tatsuaki Takeda; Hiromasa Yamamoto; Hirotaka Kanzaki; Ken Suzawa; Takahiro Yoshioka; Shuta Tomida; Xiaojiang Cui; Ramachandran Murali; Kei Namba; Hiroki Sato; Hidejiro Torigoe; Mototsugu Watanabe; Kazuhiko Shien; Junichi Soh; Hiroaki Asano; Kazunori Tsukuda; Yoshihisa Kitamura; Shinichiro Miyoshi; Toshiaki Sendo; Shinichi Toyooka
Journal:  PLoS One       Date:  2017-02-03       Impact factor: 3.240

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7.  SNP rs3202538 in 3'UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population.

Authors:  Yaxiang Shi; Xuan Chen; Biao Xi; Xiaowen Yu; Jun Ouyang; Chunxia Han; Yucheng Qin; Defeng Wu; Hong Shen
Journal:  Cancer Cell Int       Date:  2017-09-13       Impact factor: 5.722

8.  Cross-Database Analysis Reveals Sensitive Biomarkers for Combined Therapy for ERBB2+ Gastric Cancer.

Authors:  Zhen Xiang; Xia Huang; Jiexuan Wang; Jun Zhang; Jun Ji; Ranlin Yan; Zhenggang Zhu; Wei Cai; Yingyan Yu
Journal:  Front Pharmacol       Date:  2018-08-03       Impact factor: 5.810

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Authors:  Lijuan Xiong; Li Ding; Haoyong Ning; Chenglin Wu; Kaifei Fu; Yuxiao Wang; Yan Zhang; Yan Liu; Lijun Zhou
Journal:  Oncotarget       Date:  2016-09-06

10.  Nrf2 Inhibitor, Brusatol in Combination with Trastuzumab Exerts Synergistic Antitumor Activity in HER2-Positive Cancers by Inhibiting Nrf2/HO-1 and HER2-AKT/ERK1/2 Pathways.

Authors:  Yun Yang; Ziyin Tian; Rui Guo; Feng Ren
Journal:  Oxid Med Cell Longev       Date:  2020-07-19       Impact factor: 6.543
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