Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–263.
Google Scholar
Global Burden of Disease Cancer C, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study. JAMA Oncol. 2019;5:1749–1768.
Google Scholar
Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017;8:CD004064.
Google Scholar
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. 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. Lancet. 2010;376:687–697.
Google Scholar
Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. 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. Lancet Oncol. 2014;15:1224–1235.
Google Scholar
Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398:27–40.
Google Scholar
Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23:234–247.
Google Scholar
Rha SY, Oh DY, Yanez P, Bai Y, Ryu MH, Lee J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24:1181–1195.
Google Scholar
Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, et al. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022;603:942–948.
Google Scholar
Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023;402:2197–2208.
Google Scholar
Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29:2133–2141.
Google Scholar
Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401:1655–1668.
Google Scholar
Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38:1–10.
Google Scholar
Kwak Y, Kim TY, Nam SK, Hwang HJ, Han D, Oh HJ, et al. Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression. Oncologist. 2024.
Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116–129.
Google Scholar
Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer. 2017;17:318–332.
Google Scholar
Ahn S, Lee J, Hong M, Kim ST, Park SH, Choi MG, et al. FGFR2 in gastric cancer: protein overexpression predicts gene amplification and high H-index predicts poor survival. Mod Pathol. 2016;29:1095–1103.
Google Scholar
Han N, Kim MA, Lee HS, Kim WH. Evaluation of fibroblast growth factor receptor 2 expression, heterogeneity and clinical significance in gastric cancer. Pathobiology. 2015;82:269–279.
Google Scholar
Lee J, Kim ST, Kim K, Lee H, Kozarewa I, Mortimer PGS, et al. Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: the VIKTORY umbrella trial. Cancer Discov. 2019;9:1388–1405.
Google Scholar
Matsumoto K, Arao T, Hamaguchi T, Shimada Y, Kato K, Oda I, et al. FGFR2 gene amplification and clinicopathological features in gastric cancer. Br J Cancer. 2012;106:727–732.
Google Scholar
Su X, Zhan P, Gavine PR, Morgan S, Womack C, Ni X, et al. FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study. Br J Cancer. 2014;110:967–975.
Google Scholar
Rha SY, Zhang Y, Elme A, Pazo Cid R, Alacacioglu A, Ziogas DC, et al. Prevalence of FGFR2b protein overexpression in advanced gastric cancers during prescreening for the phase III FORTITUDE-101 Trial. JCO Precis Oncol. 2025;9:e2400710.
Google Scholar
Wainberg ZA, Enzinger PC, Kang YK, Qin S, Yamaguchi K, Kim IH, et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022;23:1430–1440.
Google Scholar
Catenacci DVT, Rasco D, Lee J, Rha SY, Lee KW, Bang YJ, et al. Phase I escalation and expansion study of bemarituzumab (FPA144) in patients with advanced solid tumors and FGFR2b-selected gastroesophageal adenocarcinoma. J Clin Oncol. 2020;38:2418–2426.
Google Scholar
Xiang H, Chan AG, Ahene A, Bellovin DI, Deng R, Hsu AW, et al. Preclinical characterization of bemarituzumab, an anti-FGFR2b antibody for the treatment of cancer. MAbs. 2021;13:1981202.
Google Scholar
Powers, J, Palencia, S, Foy, S, Sennino, B, Hidalgo, TR, Gemo, A, et al. FPA144, a therapeutic monoclonal antibody targeting the FGFR2b receptor, promotes antibody dependent cell-mediated cytotoxicity and stimulates sensitivity to PD-1 in the 4T1 syngeneic tumor model. Cancer Res 2016;76:1407.
Wainberg ZA, Kang YK, Lee KW, Qin S, Yamaguchi K, Kim IH, et al. Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial. Gastric Cancer. 2024;27:558–570.
Google Scholar
Lee HS. Spatial and temporal tumor heterogeneity in gastric cancer: discordance of predictive biomarkers. J Gastric Cancer. 2025;25:192–209.
Google Scholar
Lee HE, Park KU, Yoo SB, Nam SK, Park DJ, Kim HH, et al. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer. 2013;49:1448–1457.
Google Scholar
Bartley AN, Washington MK, Colasacco C, Ventura CB, Ismaila N, Benson AB, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35:446–464.
Google Scholar
Seo S, Ryu MH, Park YS, Ahn JY, Park Y, Park SR, et al. Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3). Gastric Cancer. 2019;22:527–535.
Google Scholar
Hyung J, Kim HD, Ryu MH, Park YS, Moon M, Kang YK. GASTric Cancer HER2 Re-Assessment Study 2 (GASTHER2): HER2 Re-assessment for Initially HER2-Negative Advanced Gastric Cancer Patients after Progression on First-Line Treatment. Cancer Res Treat. 2024;56:199–207.
Google Scholar
Kim TY, Kwak Y, Nam SK, Han D, Oh DY, Im SA, et al. Clinicopathological analysis of claudin 18.2 focusing on intratumoral heterogeneity and survival in patients with metastatic or unresectable gastric cancer. ESMO Open. 2024;9:104000.
Google Scholar
Ye M, Huang D, Zhang Q, Weng W, Tan C, Qin G, et al. Heterogeneous programmed death-ligand 1 expression in gastric cancer: comparison of tissue microarrays and whole sections. Cancer Cell Int. 2020;20:186.
Google Scholar
Kim KM, Bilous M, Chu KM, Kim BS, Kim WH, Park YS, et al. Human epidermal growth factor receptor 2 testing in gastric cancer. recommendations of an Asia-Pacific task force. Asia Pac J Clin Oncol. 2014;10:297–307.
Google Scholar
Fassan M, Kuwata T, Matkowskyj KA, Rocken C, Ruschoff J. Claudin-18.2 immunohistochemical evaluation in gastric and gastroesophageal junction adenocarcinomas to direct targeted therapy: a practical approach. Mod Pathol. 2024;37:100589.
Google Scholar
Park YS, Kook MC, Kim BH, Lee HS, Kang DW, Gu MJ, et al. A standardized pathology report for gastric cancer: 2nd Edition. J Gastric Cancer. 2023;23:107–145.
Google Scholar
Park Y, Nam SK, Seo SH, Park KU, Oh HJ, Park YS, et al. Comprehensive Study of Microsatellite Instability Testing and Its Comparison With Immunohistochemistry in Gastric Cancers. J Gastric Cancer. 2023;23:264–274.
Koh J, Kim J, Woo GU, Yi H, Kwon SY, Seo J, et al. Harnessing institutionally developed clinical targeted sequencing to improve patient survival in breast cancer: a seven-year experience. Cancer Res Treat (2024).
Sato S, Rhodes SL, Aoki Y, Nakayama I, Hashimoto T, Hawkins J, et al. Clinical characterization of FGFR2b expression in patients with advanced gastric or gastroesophageal junction adenocarcinoma. ESMO Open. 2025;10:105322.
Google Scholar
Lau DK, Collin JP, Mariadason JM. Clinical developments and challenges in treating FGFR2-driven gastric cancer. Biomedicines 2024;12:1117.
Das K, Gunasegaran B, Tan IB, Deng N, Lim KH, Tan P. Mutually exclusive FGFR2, HER2, and KRAS gene amplifications in gastric cancer revealed by multicolour FISH. Cancer Lett. 2014;353:167–175.
Google Scholar
Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 2012;61:673–684.
Google Scholar
Nagatsuma AK, Aizawa M, Kuwata T, Doi T, Ohtsu A, Fujii H, et al. Expression profiles of HER2, EGFR, MET and FGFR2 in a large cohort of patients with gastric adenocarcinoma. Gastric Cancer. 2015;18:227–238.
Google Scholar
