title: Therapeutic implication of HER2 in advanced biliary tract cancer.
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.
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Ah-Rong
authors: AR
authors: Nam
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Ji-Won
authors: JW
authors: Kim
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Yongjun
authors: Y
authors: Cha
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Hyerim
authors: H
authors: Ha
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Ji Eun
authors: JE
authors: Park
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Ju-Hee
authors: JH
authors: Bang
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Mei Hua
authors: MH
authors: Jin
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Kyung-Hun
authors: KH
authors: Lee
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Tae-Yong
authors: TY
authors: Kim
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Sae-Won
authors: SW
authors: Han
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Seock-Ah
authors: SA
authors: Im
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Tae-You
authors: TY
authors: Kim
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Do-Youn
authors: DY
authors: Oh
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Yung-Jue
authors: YJ
authors: Bang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage; D005704:Gallbladder / Q000000981:diagnostic imaging / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D049268:Positron-Emission Tomography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2; biliary tract cancer; gallbladder cancer; targeted therapy; trastuzumab