{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:37:56Z","timestamp":1759412276312},"reference-count":49,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","clinicaltherapeutics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Therapeutics"],"published-print":{"date-parts":[[2016,7]]},"DOI":"10.1016\/j.clinthera.2016.03.016","type":"journal-article","created":{"date-parts":[[2016,4,2]],"date-time":"2016-04-02T12:56:06Z","timestamp":1459601766000},"page":"1589-1599","update-policy":"http:\/\/dx.doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genomic Alterations and Targeted Therapy in Gastric and Esophageal Adenocarcinoma"],"prefix":"10.1016","volume":"38","clinical-trial-number":[{"clinical-trial-number":"nct01522768","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01641939","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01719549","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01774786","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02016534","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02213289","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Eirini","family":"Pectasides","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.clinthera.2016.03.016_bib1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int J Cance"},{"key":"10.1016\/j.clinthera.2016.03.016_bib2","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1158\/1055-9965.EPI-10-0012","article-title":"Esophageal adenocarcinoma incidence: are we reaching the peak?","volume":"19","author":"Pohl","year":"2010","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"10.1016\/j.clinthera.2016.03.016_bib3","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/gutjnl-2011-301839","article-title":"A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets","volume":"61","author":"Deng","year":"2012","journal-title":"Gut"},{"key":"10.1016\/j.clinthera.2016.03.016_bib4","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1056\/NEJMoa073149","article-title":"Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer","volume":"358","author":"Cunningham","year":"2008","journal-title":"N Engl J Med"},{"issue":"33","key":"10.1016\/j.clinthera.2016.03.016_bib5","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1200\/JCO.2015.60.7465","article-title":"Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium","volume":"33","author":"Shah","year":"2015","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib6","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1200\/JCO.2007.13.9378","article-title":"Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie","volume":"26","author":"Al-Batran","year":"2008","journal-title":"J Clin Onco"},{"issue":"7517","key":"10.1016\/j.clinthera.2016.03.016_bib7","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nature13480","article-title":"The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma","volume":"513","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.clinthera.2016.03.016_bib8","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.clinthera.2016.03.016_bib9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1634\/theoncologist.2014-0378","article-title":"Prospective comprehensive genomic profiling of advanced gastric carcinoma cases reveals frequent clinically relevant genomic alterations and new routes for targeted therapies","volume":"20","author":"Ali","year":"2015","journal-title":"Oncologist"},{"key":"10.1016\/j.clinthera.2016.03.016_bib10","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ng.2591","article-title":"Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity","volume":"45","author":"Dulak","year":"2013","journal-title":"Na Genet"},{"key":"10.1016\/j.clinthera.2016.03.016_bib11","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1634\/theoncologist.2015-0156","article-title":"Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences","volume":"20","author":"Wang","year":"2015","journal-title":"Oncologist"},{"issue":"4785","key":"10.1016\/j.clinthera.2016.03.016_bib12","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.3798106","article-title":"Human breast cancer: correlation of relapse and survival with amplification of the HER-2\/neu oncogene","volume":"235","author":"Slamon","year":"1987","journal-title":"Science"},{"key":"10.1016\/j.clinthera.2016.03.016_bib13","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1200\/JCO.1993.11.10.1936","article-title":"Clinical significance of HER-2\/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group","volume":"11","author":"Seshadri","year":"1993","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib14","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1093\/annonc\/mds104","article-title":"Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis","volume":"23","author":"Janjigian","year":"2012","journal-title":"An Oncol"},{"key":"10.1016\/j.clinthera.2016.03.016_bib15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/annonc\/mdi064","article-title":"Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab","volume":"16","author":"Tanner","year":"2005","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clinthera.2016.03.016_bib16","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJM200103153441101","article-title":"Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2","volume":"344","author":"Slamon","year":"2001","journal-title":"N Engl J Med"},{"issue":"9742","key":"10.1016\/j.clinthera.2016.03.016_bib17","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.clinthera.2016.03.016_bib18","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1093\/annonc\/mdr021","article-title":"Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer","volume":"22","author":"Iqbal","year":"2011","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clinthera.2016.03.016_bib19","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1200\/JCO.2015.62.6598","article-title":"Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013\/LOGiC- A Randomized Phase III Trial","volume":"34","author":"Hecht","year":"2016","journal-title":"J Clin Onco"},{"issue":"19","key":"10.1016\/j.clinthera.2016.03.016_bib20","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1200\/JCO.2013.53.6136","article-title":"Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study","volume":"32","author":"Satoh","year":"2014","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib21","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1200\/JCO.2013.48.9070","article-title":"Level of HER2 Gene Amplification Predicts Response and Overall Survival in HER2-Positive Advanced Gastric Cancer Treated With Trastuzumab","volume":"31","author":"Gomez-Martin","year":"2013","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib22","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1365-2559.2008.03021.x","article-title":"EGFR in gastric carcinomas: prognostic significance of protein overexpression and high gene copy number","volume":"52","author":"Kim","year":"2008","journal-title":"Histopathology"},{"key":"10.1016\/j.clinthera.2016.03.016_bib23","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1136\/jcp.2005.034298","article-title":"Prognostic significance of expression patterns of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor in oesophageal adenocarcinoma: a tissue microarray study","volume":"59","author":"Langer","year":"2006","journal-title":"J Clin Patho"},{"key":"10.1016\/j.clinthera.2016.03.016_bib24","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S1470-2045(13)70102-5","article-title":"Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial","volume":"14","author":"Lordick","year":"2013","journal-title":"Lancet Oncol"},{"issue":"15 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib25","first-page":"4021","article-title":"Clinical outcome according to tumor HER2 status and EGFR expression in advanced gastric cancer patients from the EXPAND study","volume":"31","author":"Lordick","year":"2013","journal-title":"ASC Meetin Abst"},{"issue":"6","key":"10.1016\/j.clinthera.2016.03.016_bib26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S1470-2045(13)70096-2","article-title":"Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial","volume":"14","author":"Waddell","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clinthera.2016.03.016_bib27","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1158\/1078-0432.CCR-06-1970","article-title":"A phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response","volume":"13","author":"Ferry","year":"2007","journal-title":"C i Cance R"},{"key":"10.1016\/j.clinthera.2016.03.016_bib28","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1200\/JCO.2005.03.4900","article-title":"Predictive factors for outcome in a phase II study of gefitinib in second-line treatment of advanced esophageal cancer patients","volume":"24","author":"Janmaat","year":"2006","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib29","doi-asserted-by":"crossref","first-page":"4922","DOI":"10.1200\/JCO.2006.07.1316","article-title":"Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127","volume":"24","author":"Dragovich","year":"2006","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib30","article-title":"A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy","volume":"3","author":"Zhang","year":"2013","journal-title":"Sci Rep"},{"key":"10.1016\/j.clinthera.2016.03.016_bib31","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/bjc.2013.802","article-title":"FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study","volume":"110","author":"Su","year":"2014","journal-title":"Br J Cance"},{"issue":"15 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib32","first-page":"4014","article-title":"A randomized, open-label phase II study of AZD4547 (AZD) versus Paclitaxel (P) in previously treated patients with advanced gastric cancer (AGC) with Fibroblast Growth Factor Receptor 2 (FGFR2) polysomy or gene amplification (amp): SHINE study","volume":"33","author":"Bang","year":"2015","journal-title":"ASC Meetin Abst"},{"key":"10.1016\/j.clinthera.2016.03.016_bib33","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1002\/(SICI)1097-0142(19990501)85:9<1894::AID-CNCR3>3.0.CO;2-J","article-title":"The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas","volume":"85","author":"Nakajima","year":"1999","journal-title":"Cancer"},{"key":"10.1016\/j.clinthera.2016.03.016_bib34","first-page":"1477","article-title":"The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation","volume":"19","author":"Drebber","year":"2008","journal-title":"Oncol Rep"},{"key":"10.1016\/j.clinthera.2016.03.016_bib35","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1158\/1055-9965.EPI-10-1080","article-title":"MET expression and amplification in patients with localized gastric cancer","volume":"20","author":"Janjigian","year":"2011","journal-title":"Cancer. Epidemiol. Biomarkers. Prev"},{"key":"10.1016\/j.clinthera.2016.03.016_bib36","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S1470-2045(14)70023-3","article-title":"Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study","volume":"15","author":"Iveson","year":"2014","journal-title":"Lancet Oncol"},{"issue":"15 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib37","first-page":"4000","volume":"33","author":"Cunningham","year":"2015","journal-title":"ASC Meetin Abstract"},{"issue":"15 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib38","first-page":"4012","article-title":"METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET+) adenocarcinoma of the stomach or gastroesophageal junction (GEC)","volume":"33","author":"Shah","year":"2015","journal-title":"ASC Meetin Abst"},{"issue":"3 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib39","first-page":"2","article-title":"Randomized phase II study of FOLFOX +\/- MET inhibitor, onartuzumab (O), in advanced gastroesophageal adenocarcinoma (GEC)","volume":"33","author":"Shah","year":"2015","journal-title":"ASC Meetin Abst"},{"issue":"3 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib40","first-page":"1","article-title":"Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer","volume":"33","author":"Kwak","year":"2015","journal-title":"ASC Meetin Abst"},{"issue":"30","key":"10.1016\/j.clinthera.2016.03.016_bib41","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1200\/JCO.2011.36.2236","article-title":"Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study","volume":"29","author":"Ohtsu","year":"2011","journal-title":"J Clin Onco"},{"issue":"17","key":"10.1016\/j.clinthera.2016.03.016_bib42","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1200\/JCO.2011.39.9824","article-title":"Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial","volume":"30","author":"Van Cutsem","year":"2012","journal-title":"J Clin Onco"},{"issue":"9911","key":"10.1016\/j.clinthera.2016.03.016_bib43","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(13)61719-5","article-title":"Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial","volume":"383","author":"Fuchs","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.clinthera.2016.03.016_bib44","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S1470-2045(14)70420-6","article-title":"Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial","volume":"15","author":"Wilke","year":"2014","journal-title":"Lancet Oncol"},{"issue":"15 suppl","key":"10.1016\/j.clinthera.2016.03.016_bib45","first-page":"4004","article-title":"Ramucirumab (RAM) plus FOLFOX as front-line therapy (Rx) for advanced gastric or esophageal adenocarcinoma (GE-AC): Randomized, double-blind, multicenter phase 2 trial","volume":"32","author":"Yoon","year":"2014","journal-title":". ASCO Meeting Abstr"},{"key":"10.1016\/j.clinthera.2016.03.016_bib46","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1172\/JCI75200","article-title":"Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma","volume":"124","author":"Kim","year":"2014","journal-title":"J Clin Inves"},{"key":"10.1016\/j.clinthera.2016.03.016_bib47","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1158\/2159-8290.CD-15-0748","article-title":"Molecular heterogeneity and receptor co-amplification drive resistance to targeted therapy in MET-amplified esophagogastric cancer","volume":"5","author":"Kwak","year":"2015","journal-title":"Cance Discov"},{"key":"10.1016\/j.clinthera.2016.03.016_bib48","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1200\/JCO.2015.63.2497","article-title":"Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer","volume":"33","author":"Kopetz","year":"2015","journal-title":"J Clin Onco"},{"key":"10.1016\/j.clinthera.2016.03.016_bib49","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1200\/JCO.2015.63.2471","article-title":"Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer","volume":"33","author":"Corcoran","year":"2015","journal-title":"J Clin Onco"}],"container-title":["Clinical Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149291816301539?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0149291816301539?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T19:51:38Z","timestamp":1536868298000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0149291816301539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7]]},"references-count":49,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["S0149291816301539"],"URL":"https:\/\/doi.org\/10.1016\/j.clinthera.2016.03.016","relation":{},"ISSN":["0149-2918"],"issn-type":[{"value":"0149-2918","type":"print"}],"subject":[],"published":{"date-parts":[[2016,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genomic Alterations and Targeted Therapy in Gastric and Esophageal Adenocarcinoma","name":"articletitle","label":"Article Title"},{"value":"Clinical Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clinthera.2016.03.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}