{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:04:53Z","timestamp":1792807493650,"version":"4.5.0"},"reference-count":81,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Priorities Research Program","award":["14S0311\u2013210033"],"award-info":[{"award-number":["14S0311\u2013210033"]}]},{"DOI":"10.13039\/100007458","name":"Qatar Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007458","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gastric and gastroesophageal junction (G\/GEJ) adenocarcinomas remain among the most aggressive and lethal malignancies globally. Most patients are diagnosed at advanced stages and respond poorly to conventional chemotherapy, highlighting the urgent demand for more effective, novel treatment strategies such as monoclonal antibody therapies targeting drivers of tumor progression. This review examines the mechanisms, safety profiles, and clinical trial outcomes of three targeted agents\u2014bemarituzumab, zolbetuximab, and ramucirumab\u2014which inhibit tumor growth through the FGFR2b, CLDN18.2, and VEGFR2 pathways, respectively. We also compare traditional versus adaptive clinical trial designs, explore emerging challenges such as therapeutic resistance and treatment-related toxicities, and consider implications for personalized medicine. Collectively, these agents represent a paradigm shift from empiric chemotherapy toward biomarker-driven immunotherapy, with the potential to significantly improve survival and quality of life in patients with advanced G\/GEJ cancers.<\/jats:p>","DOI":"10.3390\/cells14211672","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T02:50:48Z","timestamp":1761533448000},"page":"1672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5452-7842","authenticated-orcid":false,"given":"Vivian Chetachi Eziefula","family":"Njoku","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1984-6937","authenticated-orcid":false,"given":"Yein","family":"Lee","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2517-8541","authenticated-orcid":false,"given":"Joytish","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-5076","authenticated-orcid":false,"given":"Peter","family":"Kubatka","sequence":"additional","affiliation":[{"name":"Centre of Experimental and Clinical Regenerative Medicine, Small Animal Clinic, University of Veterinary Medicine and Pharmacy, 041 81 Kosice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-3366","authenticated-orcid":false,"given":"Dietrich","family":"B\u00fcsselberg","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine\u2014Qatar, Doha P.O. Box 24144, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","article-title":"Gastric cancer","volume":"396","author":"Smyth","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1158\/1055-9965.EPI-13-1057","article-title":"Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention","volume":"23","author":"Karimi","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_3","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mathias-Machado, M.C., De Jesus, V.H.F., J\u00e1come, A., Donadio, M.D., Aruquipa, M.P.S., Fogacci, J., Cunha, R.G., Silva, L.M.D., and Peixoto, R.D. (2024). Claudin 18.2 as a New Biomarker in Gastric Cancer\u2014What Should We Know?. Cancers, 16.","DOI":"10.3390\/cancers16030679"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/S1470-2045(22)00603-9","article-title":"Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study","volume":"23","author":"Wainberg","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s10120-024-01466-w","article-title":"Bemarituzumab as first-line treatment for locally advanced or metastatic gastric\/gastroesophageal junction adenocarcinoma: Final analysis of the randomized phase 2 FIGHT trial","volume":"27","author":"Wainberg","year":"2024","journal-title":"Gastric Cancer."},{"key":"ref_7","first-page":"264","article-title":"Current treatment and recent progress in gastric cancer","volume":"71","author":"Joshi","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41571-021-00492-2","article-title":"Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: An emerging paradigm","volume":"18","author":"Nakamura","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lau, D.K., Collin, J.P., and Mariadason, J.M. (2024). Clinical Developments and Challenges in Treating FGFR2-Driven Gastric Cancer. Biomedicines., 12.","DOI":"10.3390\/biomedicines12051117"},{"key":"ref_10","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_11","doi-asserted-by":"crossref","unstructured":"Yashiro, M., Kuroda, K., Masuda, G., Okuno, T., Miki, Y., Yamamoto, Y., Sera, T., Sugimoto, A., Kushiyama, S., and Nishimura, S. (2021). Clinical difference between fibroblast growth factor receptor 2 subclass, type IIIb and type IIIc, in gastric cancer. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84107-x"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s12029-025-01214-y","article-title":"FGFR as a Predictive Marker for Targeted Therapy in Gastrointestinal Malignancies: A Systematic Review","volume":"56","author":"Seraji","year":"2025","journal-title":"J. Gastrointest. Cancer."},{"key":"ref_13","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. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/jjco\/hyab104","article-title":"Cancer-related FGFR2 overexpression and gene amplification in Japanese patients with gastric cancer","volume":"51","author":"Minashi","year":"2021","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2400710","DOI":"10.1200\/PO-24-00710","article-title":"Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial","volume":"9","author":"Rha","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1981202","DOI":"10.1080\/19420862.2021.1981202","article-title":"Preclinical characterization of bemarituzumab, an anti-FGFR2b antibody for the treatment of cancer","volume":"13","author":"Xiang","year":"2021","journal-title":"mAbs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s13046-024-03217-2","article-title":"The FGF\/FGFR\/c-Myc axis as a promising therapeutic target in multiple myeloma","volume":"43","author":"Giacomini","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_18","first-page":"163","article-title":"FGF signaling network in the gastrointestinal tract (Review)","volume":"29","author":"Katoh","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ferguson, H.R., Smith, M.P., and Francavilla, C. (2021). Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling. Cells, 10.","DOI":"10.3390\/cells10051201"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Szymczyk, J., Sluzalska, K.D., Materla, I., Opalinski, L., Otlewski, J., and Zakrzewska, M. (2021). FGF\/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance. Cancers, 13.","DOI":"10.3390\/cancers13225796"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.3892\/ijo.2017.3927","article-title":"FGF7\/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1","volume":"50","author":"Huang","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Grizzi, G., Venetis, K., Denaro, N., Bonomi, M., Celotti, A., Pagkali, A., Hahne, J.C., Tomasello, G., Petrelli, F., and Fusco, N. (2023). Anti-Claudin Treatments in Gastroesophageal Adenocarcinoma: Mainstream and Upcoming Strategies. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082973"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100712","DOI":"10.1016\/j.modpat.2025.100712","article-title":"Claudin 18.2 Expression in 1404 Digestive Tract Adenocarcinomas Including 1175 Colorectal Carcinomas: Distinct Colorectal Carcinoma Subtypes Are Claudin 18.2 Positive","volume":"38","author":"McHugh","year":"2025","journal-title":"Mod Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100589","DOI":"10.1016\/j.modpat.2024.100589","article-title":"Claudin-18.2 Immunohistochemical Evaluation in Gastric and Gastroesophageal Junction Adenocarcinomas to Direct Targeted Therapy: A Practical Approach","volume":"37","author":"Fassan","year":"2024","journal-title":"Mod. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.annonc.2021.02.005","article-title":"FAST: A randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma","volume":"32","author":"Sahin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jphs.2024.04.004","article-title":"Effect of anti-claudin 18.2 monoclonal antibody zolbetuximab alone or combined with chemotherapy or programmed cell death-1 blockade in syngeneic and xenograft gastric cancer models","volume":"155","author":"Nishibata","year":"2024","journal-title":"J. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1007\/s10120-024-01518-1","article-title":"Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma","volume":"27","author":"Shitara","year":"2024","journal-title":"Gastric Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s40425-018-0403-1","article-title":"Targeting VEGFR2 with Ramucirumab strongly impacts effector\/ activated regulatory T cells and CD8+ T cells in the tumor microenvironment","volume":"6","author":"Tada","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6973","DOI":"10.21873\/anticanres.13919","article-title":"Clinical Implications of Claudin18.2 Expression in Patients With Gastric Cancer","volume":"39","author":"Baek","year":"2019","journal-title":"Anticancer. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12964-023-01406-8","article-title":"Claudin-18.2 mediated interaction of gastric Cancer cells and Cancer-associated fibroblasts drives tumor progression","volume":"22","author":"Liu","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e34611","DOI":"10.1016\/j.heliyon.2024.e34611","article-title":"A novel highly sensitive inner filter effect-based fluorescence immunoassay with quantum dots for bioanalysis of zolbetuximab, a monoclonal antibody used for immunotherapy of gastric and gastroesophageal junction adenocarcinoma","volume":"10","author":"Darwish","year":"2024","journal-title":"Heliyon"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liang, Z., Liu, L., Li, W., Lai, H., Li, L., Wu, J., Zhang, H., and Fang, C. (2023). Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1258347"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/annonc\/mdz199","article-title":"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":"Sahin","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1007\/s00432-022-04459-3","article-title":"Immunological effects and activity of multiple doses of zolbetuximab in combination with zoledronic acid and interleukin-2 in a phase 1 study in patients with advanced gastric and gastroesophageal junction cancer","volume":"149","author":"Lordick","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejca.2022.01.015","article-title":"FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel\u2014results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO","volume":"165","author":"Lorenzen","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_36","first-page":"e75206","article-title":"Zolbetuximab for Unresectable and Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma: A Review of Literature","volume":"16","author":"Samanta","year":"2024","journal-title":"Cureus"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13045-022-01310-7","article-title":"Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy","volume":"15","author":"Liu","year":"2022","journal-title":"J. Hematol. Oncol. J. Hematol. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lian, L., Li, X.L., Xu, M.D., Li, X.M., Wu, M.Y., Zhang, Y., Tao, M., Li, W., Shen, X.-M., and Zhou, C. (2019). VEGFR2 promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5322-0"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jb\/mvs136","article-title":"Vascular endothelial growth factor and its receptor system: Physiological functions in angiogenesis and pathological roles in various diseases","volume":"153","author":"Shibuya","year":"2013","journal-title":"J. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.cellsig.2007.05.013","article-title":"Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition","volume":"19","author":"Holmes","year":"2007","journal-title":"Cell Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11990","DOI":"10.18632\/oncotarget.14467","article-title":"Autocrine VEGF signaling promotes cell proliferation through a PLC-dependent pathway and modulates Apatinib treatment efficacy in gastric cancer","volume":"8","author":"Lin","year":"2017","journal-title":"Oncotarget."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.prp.2018.02.005","article-title":"VEGFR-2 as a novel predictor of survival in gastric cancer: A systematic review and meta-analysis","volume":"214","author":"Li","year":"2018","journal-title":"Pathol. Res. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4062\/biomolther.2013.113","article-title":"VEGF-VEGFR Signals in Health and Disease","volume":"22","author":"Shibuya","year":"2014","journal-title":"Biomol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1200\/JCO.2009.23.7537","article-title":"Phase I Pharmacologic and Biologic Study of Ramucirumab (IMC-1121B), a Fully Human Immunoglobulin G1 Monoclonal Antibody Targeting the Vascular Endothelial Growth Factor Receptor-2","volume":"28","author":"Spratlin","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0140-6736(15)01088-0","article-title":"Antiangiogenic therapy in oncology: Current status and future directions","volume":"388","author":"Jayson","year":"2016","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, X., Bove, A.M., Simone, G., and Ma, B. (2020). Molecular Bases of VEGFR-2-Mediated Physiological Function and Pathological Role. Front Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.599281"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrm1911","article-title":"VEGF receptor signalling? In control of vascular function","volume":"7","author":"Olsson","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/j.1349-7006.2003.tb01514.x","article-title":"Vascular endothelial growth factor receptor-2: Its unique signaling and specific ligand, VEGF-E","volume":"94","author":"Shibuya","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.molmed.2010.01.004","article-title":"Use of anti-VEGF adjuvant therapy in cancer: Challenges and rationale","volume":"16","author":"Bagri","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"D\u2019Alessandro, R., Refolo, M.G., Schirizzi, A., De Leonardis, G., Donghia, R., Guerra, V., Giannelli, G., Lolli, I.R., Laterza, M.M., and De Vita, F. (2022). Variations in Circulating Levels of Angiopoietin-2 Over Time Are Predictive of Ramucirumab\u2013Paclitaxel Therapy Outcome in Advanced Gastric Cancer: Results of Prospective Study. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.862116"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1200\/JCO.19.01834","article-title":"Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients with Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma","volume":"38","author":"Catenacci","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105322","DOI":"10.1016\/j.esmoop.2025.105322","article-title":"Clinical characterization of FGFR2b expression in patients with advanced gastric or gastroesophageal junction adenocarcinoma","volume":"10","author":"Sato","year":"2025","journal-title":"ESMO Open"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1158\/1078-0432.CCR-23-0204","article-title":"ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2\u2013Positive Gastric or Gastroesophageal Junction Adenocarcinoma","volume":"29","author":"Klempner","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"103663","DOI":"10.1016\/j.esmoop.2024.103663","article-title":"Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: Results from the SPOTLIGHT and GLOW clinical trials","volume":"9","author":"Lordick","year":"2024","journal-title":"ESMO Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3390\/curroncol31020057","article-title":"Evidence to Date on the Therapeutic Potential of Zolbetuximab in Advanced Gastroesophageal Adenocarcinoma","volume":"31","author":"Rogers","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s10120-020-01153-6","article-title":"Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma","volume":"24","author":"Lordick","year":"2021","journal-title":"Gastric Cancer."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s10120-017-0745-2","article-title":"Safety, pharmacokinetic, and clinical activity profiles of ramucirumab in combination with three platinum\/fluoropyrimidine doublets in Japanese patients with chemotherapy-na\u00efve metastatic gastric\/gastroesophageal junction cancer","volume":"21","author":"Shitara","year":"2018","journal-title":"Gastric Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1111\/cas.15684","article-title":"Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma","volume":"114","author":"Shitara","year":"2023","journal-title":"Cancer Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S1530","DOI":"10.1016\/j.annonc.2023.10.281","article-title":"146P Phase (ph) Ib results of bemarituzumab (BEMA) added to capecitabine\/oxaliplatin (CAPOX) or S-1\/oxaliplatin (SOX) with or without nivolumab (NIVO) for previously untreated advanced gastric\/gastroesophageal junction cancer (G\/GEJC): FORTITUDE-103 study","volume":"34","author":"Lee","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/14737140.2025.2463493","article-title":"Contemporary management of advanced gastric and gastroesophageal adenocarcinomas","volume":"25","author":"Rogers","year":"2025","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41416-023-02534-1","article-title":"NCI10066: A Phase 1\/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma","volume":"130","author":"Cecchini","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"De Moraes, F.C.A., Pasqualotto, E., Chavez, M.P., Ferreira, R.O.M., De Castria, T.B., and Burbano, R.M.R. (2024). Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: A meta-analysis of randomized clinical trials. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-11980-w"},{"key":"ref_64","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 Lond. Engl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1080\/14622416.2024.2344438","article-title":"The cost\u2013effectiveness of zolbetuximab in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma","volume":"25","author":"Lai","year":"2024","journal-title":"Pharmacogenomics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"100189","DOI":"10.1016\/j.esmogo.2025.100189","article-title":"WJOG18524G: A single-arm phase II study evaluating bemarituzumab combined with ramucirumab and paclitaxel in fibroblast growth factor receptor 2b (FGFR2b)-positive advanced gastric or gastroesophageal junction cancer (RAINBIRD)","volume":"9","author":"Shimozaki","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1093\/annonc\/mdw423","article-title":"Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: A randomized, double-blind, multicenter Phase II trial","volume":"27","author":"Yoon","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_68","unstructured":"Ryan, C., and OncLive (MJH Life Sciences) (2025, August 30). First-Line Bemarituzumab Plus Chemo Hits OS End Point in FGFR2b+ Advanced Gastric Cancer. Available online: https:\/\/www.onclive.com\/view\/first-line-bemarituzumab-plus-chemo-hits-os-end-point-in-fgfr2b-advanced-gastric-cancer?utm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: The randomized, phase 3 GLOW trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Huang, Y., You, M., Wu, Q., and Chen, R. (2023). Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or Gastroesophageal Adenocarcinoma. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1238009"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s40265-024-02056-x","article-title":"Zolbetuximab: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"ref_72","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_73","doi-asserted-by":"crossref","first-page":"17562848241297052","DOI":"10.1177\/17562848241297052","article-title":"First-line treatment with zolbetuximab plus CAPOX for ClDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: A cost-effectiveness analysis","volume":"17","author":"Lei","year":"2024","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Choi, E., Shin, J., Ryu, M.H., Kim, H.D., and Park, Y.S. (2024). Heterogeneity of claudin 18.2 expression in metastatic gastric cancer. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-68411-w"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/bjc.2016.30","article-title":"Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: Results from the randomised phase III AVAGAST trial","volume":"114","author":"Hacker","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41389-019-0145-z","article-title":"A functional CRISPR\/Cas9 screen identifies kinases that modulate FGFR inhibitor response in gastric cancer","volume":"8","author":"Chen","year":"2019","journal-title":"Oncogenesis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ichikawa, K., Watanabe Miyano, S., Minoshima, Y., Matsui, J., and Funahashi, Y. (2020). Activated FGF2 signaling pathway in tumor vasculature is essential for acquired resistance to anti-VEGF therapy. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59853-z"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s40123-025-01139-6","article-title":"Advancing Ocular Safety Profile Assessment: A Novel Grading Scale for Ocular Adverse Reactions Associated with Bemarituzumab","volume":"14","author":"Farooq","year":"2025","journal-title":"Ophthalmol Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jphs.2024.08.005","article-title":"Effect of antiemetics on zolbetuximab-induced gastric injury and emesis in ferrets","volume":"156","author":"Kinugasa","year":"2024","journal-title":"J. Pharmacol. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chiba, T., Ujiie, H., Yaegashi, Y., Umehara, K., Takada, S., Otaki, K., Sako, K.-I., Nakamaru, Y., Maeda, T., and Kudo, K. (2022). Reninangiotensin system inhibitors may have an advantage over calcium channel blockers in reducing proteinuria in gastric cancer patients receiving ramucirumab. Biomed. Rep., 17.","DOI":"10.3892\/br.2022.1559"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1177\/1078155217707335","article-title":"Cost-effectiveness and safety of ramucirumab plus paclitaxel chemotherapy in the treatment of advanced and recurrent gastric cancer","volume":"24","author":"Kimura","year":"2018","journal-title":"J. Oncol. Pharm. Pract."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1672\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:24:04Z","timestamp":1761629044000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/21\/1672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,26]]},"references-count":81,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cells14211672"],"URL":"https:\/\/doi.org\/10.3390\/cells14211672","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,26]]}}}