{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:29:23Z","timestamp":1770460163278,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/02180"],"award-info":[{"award-number":["PI15\/02180"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01909"],"award-info":[{"award-number":["PI18\/01909"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Rio Hortega contract CM18\/00241"],"award-info":[{"award-number":["Rio Hortega contract CM18\/00241"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Rio Hortega contract CM15\/00246"],"award-info":[{"award-number":["Rio Hortega contract CM15\/00246"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Joan Rodes contract 17\/00026"],"award-info":[{"award-number":["Joan Rodes contract 17\/00026"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["Joan Rodes contract 16\/00040"],"award-info":[{"award-number":["Joan Rodes contract 16\/00040"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Gastroesophageal adenocarcinoma (GEA) represents a heterogeneous disease and, when diagnosed as locally advanced or metastatic, it is characterized by poor prognosis. During the last few years, several molecular classifications have been proposed to try to personalize treatment for those patients diagnosed with advanced disease. Nevertheless, despite the great effort, precision medicine is still far from being a reality. The improvement in the molecular analysis due to the application of high throughput technologies based on DNA and RNA sequencing has opened a novel scenario leading to the personalization of treatment. The possibility to target epidermal growth factor receptor (HER)2, Claudine, Fibroblast Growth Factor Receptors (FGFR), and other alterations with a molecular matched therapy could significantly improve clinical outcomes over advanced gastric cancer patients. On the other hand, the development of immunotherapy could also represent a promising strategy in a selected population. In this review, we sought to describe the novel pathways implicated in GEA progression and the results of the molecular matched therapies.<\/jats:p>","DOI":"10.3390\/jcm9093049","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"3049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Precision Medicine to Treat Advanced Gastroesophageal Adenocarcinoma: A Work in Progress"],"prefix":"10.3390","volume":"9","author":[{"given":"Valentina","family":"Gambardella","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"},{"name":"Instituto de Salud Carlos III, CIBERONC, 28000 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Fleitas","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"},{"name":"Instituto de Salud Carlos III, CIBERONC, 28000 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Tarazona","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"},{"name":"Instituto de Salud Carlos III, CIBERONC, 28000 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-8696","authenticated-orcid":false,"given":"Federica","family":"Papaccio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisol","family":"Huerta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-4130","authenticated-orcid":false,"given":"Susana","family":"Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Gimeno-Valiente","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desamparados","family":"Roda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"},{"name":"Instituto de Salud Carlos III, CIBERONC, 28000 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-3691","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Cervantes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Blasco Iba\u00f1ez 17, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., and Jemal, A. (2018). Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin., 394\u2013424.","DOI":"10.3322\/caac.21492"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nagaraja, A.K., Kikuchi, O., and Bass, A.J. (2019). Genomics and Targeted Therapies in Gastroesophageal Adenocarcinoma. Cancer Discov.","DOI":"10.1158\/2159-8290.CD-19-0487"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/jnci\/djx262","article-title":"The Changing Face of Noncardia Gastric Cancer Incidence among US Non-Hispanic Whites","volume":"110110","author":"Anderson","year":"2018","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1136\/gutjnl-2014-308252","article-title":"Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas","volume":"64","author":"Lin","year":"2015","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ctrv.2012.09.007","article-title":"Current questions for the treatment of advanced gastric cancer","volume":"3939","author":"Cervantes","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.ctrv.2014.03.002","article-title":"Unmet needs and challenges in gastric cancer: The way forward","volume":"4040","author":"Lordick","year":"2014","journal-title":"Cancer Treat. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa055531","article-title":"Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer","volume":"355355","author":"Cunningham","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","first-page":"1948","article-title":"Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2\/3 trial","volume":"393393","author":"Homann","year":"2019","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513, 202\u2013209.","DOI":"10.1038\/nature13480"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nm.3850","article-title":"Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes","volume":"21","author":"Cristescu","year":"2015","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sohn, B.H., Hwang, J.-E., Jang, H.-J., Lee, H.S., Oh, S.C., Shim, J.J., Lee, K.W., Kim, E.H., Yim, S.Y., and Lee, S.H. (2017). Clinical Significance of Four Molecular Subtypes of Gastric Cancer Identified by The Cancer Genome Atlas Project. Clin. Cancer Res. J. Am. Assoc. Cancer Res.","DOI":"10.1158\/1078-0432.CCR-16-2211"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1158\/2159-8290.CD-17-0395","article-title":"Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma","volume":"8","author":"Pectasides","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ccr.2014.02.025","article-title":"ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics","volume":"25","author":"Arteaga","year":"2014","journal-title":"Cancer Cell."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1093\/annonc\/mdz143","article-title":"Towards precision oncology for HER2 blockade in gastroesophageal adenocarcinoma","volume":"30","author":"Gambardella","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e8437","DOI":"10.1097\/MD.0000000000008437","article-title":"Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis","volume":"96","author":"Wang","year":"2017","journal-title":"Medicine (Baltimore)"},{"key":"ref_18","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 treatmentof 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":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11912-016-0525-x","article-title":"Personalised Treatment in Gastric Cancer: Myth or Reality?","volume":"18","author":"Tarazona","year":"2016","journal-title":"Curr. Oncol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sicklick, J.K., Kato, S., Okamura, R., Schwaederle, M., Hahn, M.E., Williams, C.B., De, P., Krie, A., Piccioni, D.E., and Miller, V.A. (2019). Molecular profiling of cancer patients enables personalized combination therapy: The I-PREDICT study. Nat. Med.","DOI":"10.1038\/s41591-019-0407-5"},{"key":"ref_21","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":"Plaza","year":"2013","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_22","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\u2014A Randomized Phase III Trial","volume":"34","author":"Hecht","year":"2016","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_23","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\u2014A randomized, phase III study","volume":"32","author":"Satoh","year":"2014","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/S1470-2045(18)30481-9","article-title":"Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): Final analysis of a double-blind, randomised, placebo-controlled phase 3 study","volume":"19","author":"Tabernero","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/S1470-2045(17)30111-0","article-title":"Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): An international randomised, open-label, adaptive, phase 2\/3 study","volume":"18","author":"Shah","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1200\/JCO.19.03077","article-title":"Original reports abstract Randomized Phase II Study of Trastuzumab Beyond Progression in Patients with HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study)","volume":"38","author":"Makiyama","year":"2020","journal-title":"J. Clin. Onciol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1002\/ijc.30408","article-title":"HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy: Implication for further clinical research","volume":"139","author":"Pietrantonio","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1158\/1078-0432.CCR-18-2421","article-title":"Nrf2 through RPs6 activation is related to anti-HER2 drug resistance in HER2-amplified gastric cancer","volume":"25","author":"Gambardella","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1158\/2159-8290.CD-17-0787","article-title":"Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer","volume":"8","author":"Janjigian","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/annonc\/mdy034","article-title":"Impact of genomic alterations on lapatinib treatment outcome and cell-free genomic landscape during HER2 therapy in HER2+ gastric cancer patients","volume":"29","author":"Kim","year":"2018","journal-title":"Ann. Oncol. J. Eur. Soc. Med. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1093\/annonc\/mdx002","article-title":"First-in-human phase 1 study of margetuximab antibody, in patients with HER2-positive advanced solid tumors","volume":"28","author":"Bang","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_32","first-page":"1","article-title":"Articles Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal phase 1b-2 trial","volume":"2045","author":"Catenacci","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1470-2045(18)30812-X","article-title":"Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): A single-arm, multicentre, phase 1b-2 trial","volume":"20","author":"Loi","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1158\/1078-0432.CCR-15-2021","article-title":"Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer","volume":"22","author":"Varadan","year":"2016","journal-title":"Clin. Cancer Res. J. Am. Assoc. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5133","DOI":"10.1158\/1078-0432.CCR-07-0507","article-title":"Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy","volume":"13","author":"Taylor","year":"2007","journal-title":"Clin. Cancer Res. J. Am. Assoc. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ccr.2010.06.014","article-title":"The therapeutic effect of anti-HER2\/neu antibody depends on both innate and adaptive immunity","volume":"18","author":"Park","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e180013","DOI":"10.1001\/jamaoncol.2018.0013","article-title":"Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial","volume":"4","author":"Fuchs","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S1470-2045(20)30169-8","article-title":"First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: An open-label, single-arm, phase 2 trial","volume":"21","author":"Janjigian","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1158\/1078-0432.CCR-15-2822","article-title":"DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1","volume":"22","author":"Ogitani","year":"2016","journal-title":"Clin. Cancer Res. J. Am. Assoc. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1080\/00498254.2018.1531158","article-title":"Comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, in cynomolgus monkeys","volume":"49","author":"Nagai","year":"2019","journal-title":"Xenobiotica"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/nrc1949","article-title":"Cysteine cathepsins: Multifunctional enzymes in cancer","volume":"6","author":"Mohamed","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/cas.12966","article-title":"Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity","volume":"107","author":"Ogitani","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_43","first-page":"57","article-title":"HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value\u2014Conclusions from 924 cases of two independent series","volume":"32","author":"Grabsch","year":"2010","journal-title":"Cell Oncol. J. Int. Soc. Cell Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/S1470-2045(17)30604-6","article-title":"Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody\u2013drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: A phase 1 dose-escalation study","volume":"18","author":"Doi","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1056\/NEJMoa2004413","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer","volume":"382","author":"Shitara","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1002\/ijc.32408","article-title":"[fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification","volume":"145","author":"Takegawa","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/pro.2666","article-title":"Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate","volume":"24","author":"Marcoux","year":"2015","journal-title":"Protein Sci."},{"key":"ref_48","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":"ref_49","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1158\/2159-8290.CD-17-1260","article-title":"Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma","volume":"8","author":"Maron","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_50","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."},{"key":"ref_51","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":"ref_52","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S1470-2045(14)70024-5","article-title":"Gefitinib for oesophageal cancer progressing after chemotherapy (COG): A phase 3, multicentre, double-blind, placebo-controlled randomised trial","volume":"15","author":"Dutton","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1001\/jamaoncol.2016.5580","article-title":"Effect of Fluorouracil, Leucovorin, and Oxaliplatin With or Without Onartuzumab in HER2-Negative, MET-Positive Gastroesophageal Adenocarcinoma: The METGastric Randomized Clinical Trial","volume":"3","author":"Shah","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S1470-2045(17)30566-1","article-title":"Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"18","author":"Catenacci","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1158\/1078-0432.CCR-18-1337","article-title":"A Multicenter Phase II Study of AMG 337 in Patients with MET-Amplified Gastric\/Gastroesophageal Junction\/Esophageal Adenocarcinoma and Other MET-Amplified Solid Tumors","volume":"25","author":"Karaszewska","year":"2019","journal-title":"Clin. Cancer Res. J. Am. Assoc. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1200\/JCO.2012.48.3552","article-title":"Everolimus for previously treated advanced gastric cancer: Results of the randomized, double-blind, phase III GRANITE-1 study","volume":"31","author":"Ohtsu","year":"2013","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1158\/2159-8290.CD-19-0442","article-title":"Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial","volume":"9","author":"Lee","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1158\/1078-0432.CCR-17-2469","article-title":"Andecaliximab\/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study","volume":"24","author":"Shah","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_60","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. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1470-2045(18)30791-5","article-title":"Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"20","author":"Fuchs","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_62","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":"ref_63","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."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1200\/JCO.2015.63.5995","article-title":"Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients with Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction","volume":"34","author":"Li","year":"2016","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(17)31827-5","article-title":"Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"Kang","year":"2017","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1200\/JCO.2017.76.6212","article-title":"CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer","volume":"36","author":"Janjigian","year":"2018","journal-title":"J. Clin. Oncol. J. Am. Soc. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1038\/s41591-018-0101-z","article-title":"Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer","volume":"24","author":"Kim","year":"2018","journal-title":"Nat. Med."},{"key":"ref_68","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":"ref_69","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1007\/s10120-018-0851-9","article-title":"Transcriptional analysis of immune genes in Epstein-Barr virus-associated gastric cancer and association with clinical outcomes","volume":"21","author":"Sundar","year":"2018","journal-title":"Gastric Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1093\/annonc\/mdy550","article-title":"Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer","volume":"30","author":"Sundar","year":"2019","journal-title":"Ann. Oncol. J. Eur. Soc. Med. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/annonc\/mdz008","article-title":"Understanding mechanisms of primary resistance to checkpoint inhibitors will lead to precision immunotherapy of advanced gastric cancer","volume":"30","author":"Gambardella","year":"2019","journal-title":"Ann. Oncol. J. Eur. Soc. Med. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/S1470-2045(20)30271-0","article-title":"Articles Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting","volume":"21","author":"Kawazoe","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_73","first-page":"1","article-title":"Comment Lenvatinib and pembrolizumab in advanced gastric cancer","volume":"2045","author":"Cascinu","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1200\/JCO.19.03296","article-title":"Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)","volume":"38","author":"Fukuoka","year":"2020","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7624","DOI":"10.1158\/1078-0432.CCR-08-1547","article-title":"Human Cancer Biology Claudin-18 Splice Variant 2 Is a Pan-Cancer T arget Suitable for Therapeutic Antibody Development","volume":"14","author":"Sahin","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ejca.2018.05.007","article-title":"ScienceDirect A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer *","volume":"100","author":"Sahin","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/annonc\/mdz199","article-title":"Original article a multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: The MONO study","volume":"30","author":"Tu","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1093\/annonc\/mdt419","article-title":"Genomic aberrations in the FGFR pathway: Opportunities for targeted therapies in solid tumors","volume":"25","author":"Dienstmann","year":"2014","journal-title":"Ann. Oncol. J. Eur. Soc. Med. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nrc.2017.8","article-title":"Advances and challenges in targeting FGFR signalling in cancer","volume":"17","author":"Babina","year":"2017","journal-title":"Nat. Rev. Cancer."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Gambardella, V., Tarazona, N., Cejalvo, J.M., Lombardi, P., Huerta, M., Rosell\u00f3, S., Fleitas, T., Roda, D., and Cervantes, A. (2020). Personalized Medicine: Recent Progress in Cancer Therapy. Cancers, 12.","DOI":"10.3390\/cancers12041009"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","article-title":"Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study","volume":"21","author":"Sahai","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/S1470-2045(19)30412-7","article-title":"Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: A phase 1 dose-escalation and dose-expansion study","volume":"20","author":"Schuler","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bahleda, R., Meric-Bernstam, F., Goyal, L., Tran, B., He, Y., Yamamiya, I., Benhadji, K.A., Matos, I., and Arkenau, H.T. (2020). Phase 1, First-in-Human Study of Futibatinib, a Highly Selective, Irreversible FGFR1-4 Inhibitor in Patients with Advanced Solid Tumors. Ann. Oncol. J. Eur. Soc. Med. Oncol.","DOI":"10.1016\/j.annonc.2020.06.018"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1158\/1078-0432.CCR-18-3334","article-title":"Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors","volume":"25","author":"Bahleda","year":"2019","journal-title":"Clin. Cancer Res. J. Am. Assoc. Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/modpathol.2016.96","article-title":"FGFR2 in gastric cancer: Protein overexpression predicts gene amplification and high H-index predicts poor survival","volume":"29","author":"Ahn","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Zhang, J., Tang, P.M.K., Zhou, Y., Cheng, A.S.-L., Yu, J., Kang, W., and To, K.F. (2019). Targeting the Oncogenic FGF-FGFR Axis in Gastric Carcinogenesis. Cells, 8.","DOI":"10.3390\/cells8060637"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5366","DOI":"10.1158\/1078-0432.CCR-17-0645","article-title":"A phase Ib open-label multicenter study of AZD4547 in patients with advanced squamous cell lung cancers","volume":"23","author":"Paik","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1093\/annonc\/mdx107","article-title":"A randomized, open-label study of the efficacy and safety of AZD4547 monotherapy versus paclitaxel for the treatment of advanced gastric adenocarcinoma with FGFR2 polysomy or gene amplification","volume":"28","author":"Bang","year":"2017","journal-title":"Ann. Oncol. J. Eur. Soc. Med. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.2217\/fon-2019-0141","article-title":"Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design","volume":"15","author":"Catenacci","year":"2019","journal-title":"Future Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1200\/JCO.2014.60.0320","article-title":"Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer","volume":"33","author":"Bang","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1016\/S1470-2045(17)30682-4","article-title":"Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"18","author":"Bang","year":"2017","journal-title":"Lancet Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/9\/3049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:16Z","timestamp":1760177536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/9\/3049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":91,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["jcm9093049"],"URL":"https:\/\/doi.org\/10.3390\/jcm9093049","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]}}}