Low positivity rate of fibroblast growth factor receptor 2b is associated with heterogeneous expression in gastric cancer

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;74:229–63.

Article  PubMed  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;376:687–97.

Article  CAS  PubMed  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.

Article  CAS  PubMed  PubMed Central  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;401:1655–68.

Article  CAS  PubMed  Google Scholar 

Shah MA, Shitara K, Ajani JA, Bang Y-J, 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;29:2133–41.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rha SY, Oh D-Y, Yañez P, Bai Y, Ryu M-H, 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;24:1181–95.

Article  CAS  PubMed  Google Scholar 

Xu J, Jiang H, Pan Y, Gu K, Cang S, Han L, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer: the ORIENT-16 randomized clinical trial. JAMA. 2023;330:2064–74.

Article  PubMed  PubMed Central  Google Scholar 

Moehler MH, Kato K, Arkenau H-T, Oh D-Y, Tabernero J, Cruz-Correa M, et al. Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). J Clin Oncol. 2023;41:286.

Article  Google Scholar 

Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012;18:1855–62.

Article  CAS  PubMed  Google Scholar 

Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–49.

Article  CAS  PubMed  Google Scholar 

Yashiro M, Kuroda K, Masuda G, Okuno T, Miki Y, Yamamoto Y, et al. Clinical difference between fibroblast growth factor receptor 2 subclass, type IIIb and type IIIc, in gastric cancer. Sci Rep. 2021;11:4698.

Article  CAS  PubMed  PubMed Central  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.

Article  PubMed  PubMed Central  Google Scholar 

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;27:558–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kang Y-K, Qin S, Lee K-W, Oh SC, Kim I-H, Kim JG, et al. Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis. Gastric Cancer. 2024;27:1046–57.

Article  CAS  PubMed  PubMed Central  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;82:269–79.

Article  CAS  PubMed  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;29:1095–103.

Article  CAS  PubMed  Google Scholar 

Kim HS, Kim JH, Jang HJ, Han B, Zang DY. Pathological and prognostic impacts of FGFR2 overexpression in gastric cancer: a meta-analysis. J Cancer. 2019;10:20–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hosoda K, Yamashita K, Ushiku H, Ema A, Moriya H, Mieno H, et al. Prognostic relevance of FGFR2 expression in stage II/III gastric cancer with curative resection and S-1 chemotherapy. Oncol Lett. 2018;15:1853–60.

PubMed  Google Scholar 

Schrumpf T, Behrens HM, Haag J, Krüger S, Röcken C. FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort. PLoS ONE. 2022;17: e0264011.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Park YS, Na YS, Ryu MH, Lee CW, Park HJ, Lee JK, et al. FGFR2 assessment in gastric cancer using quantitative real-time polymerase chain reaction, fluorescent in situ hybridization, and immunohistochemistry. Am J Clin Pathol. 2015;143:865–72.

Article  CAS  PubMed  Google Scholar 

Kim H-D, Choi E, Shin J, Lee I-S, Ko CS, Ryu M-H, et al. Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer. Sci Rep. 2023;13:20047.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim H-D, Ryu M-H, Park YS, Lee SY, Moon M, Kang Y-K. Insertion–deletion rate is a qualitative aspect of the tumor mutation burden associated with the clinical outcomes of gastric cancer patients treated with nivolumab. Gastric Cancer. 2022;25:226–34.

Article  CAS  PubMed  Google Scholar 

Hofmann M, Stoss O, Shi D, Büttner R, Van De Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

Article  CAS  PubMed  Google Scholar 

Hashimoto T, Nakamura Y, Mishima S, Nakayama I, Kotani D, Kawazoe A, et al. Whole-transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential. Cancer Sci. 2024;115:1622–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016;22:4619–25.

Article  CAS  PubMed  PubMed Central  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;23:1430–40.

Article  CAS  PubMed  Google Scholar 

Tokunaga R, Imamura Y, Nakamura K, Ishimoto T, Nakagawa S, Miyake K, et al. Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma. Oncotarget. 2016;7:19748–61.

Article  PubMed  PubMed Central  Google Scholar 

Sato S, Rhodes SL, Aoki Y, Nakayama I, Hashimoto T, Finger E, et al. 1420P Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression and biomarker overlap in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC). Ann Oncol. 2024;35:S885-6.

Article  Google Scholar 

Combs SE, Han G, Mani N, Beruti S, Nerenberg M, Rimm DL. Loss of antigenicity with tissue age in breast cancer. Lab Invest. 2016;96:264–9.

Article 

Comments (0)

No login
gif