Oncotarget

Research Papers:

Therapeutic implication of HER2 in advanced biliary tract cancer

Ah-Rong Nam, Ji-Won Kim, Yongjun Cha, Hyerim Ha, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Do-Youn Oh _ and Yung-Jue Bang

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Oncotarget. 2016; 7:58007-58021. https://doi.org/10.18632/oncotarget.11157

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Abstract

Ah-Rong Nam1,*, Ji-Won Kim2,*, Yongjun Cha1,3, Hyerim Ha3, Ji Eun Park1, Ju-Hee Bang1, Mei Hua Jin1, Kyung-Hun Lee1,3, Tae-Yong Kim1, Sae-Won Han1,3, Seock-Ah Im1,3, Tae-You Kim1,3, Do-Youn Oh1,3, Yung-Jue Bang1,3

1Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

3Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

*These authors contributed equally to this work

Correspondence to:

Do-Youn Oh, email: [email protected]

Keywords: HER2, biliary tract cancer, gallbladder cancer, trastuzumab, targeted therapy

Received: February 18, 2016     Accepted: July 27, 2016     Published: August 09, 2016

ABSTRACT

Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC.


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