FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma

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Authors: Elizabeth C Smyth ; Kyoung-Mee Kim ; Sun Young Rha ; Zev A Wainberg ; Hayden Honeycutt ; Erica Sommermann ; Atsushi Ochiai

MeSH: Adenocarcinoma* / drug therapy ; Adenocarcinoma* / genetics ; Adenocarcinoma* / metabolism ; Adenocarcinoma* / pathology ; Biomarkers, Tumor* / genetics ; Biomarkers, Tumor* / metabolism ; Esophageal Neoplasms* / drug therapy ; Esophageal Neoplasms* / genetics ; Esophageal Neoplasms* / metabolism ; Esophageal Neoplasms* / pathology ; Esophagogastric Junction* / metabolism ; Esophagogastric Junction* / pathology ; Humans ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 2* / genetics ; Receptor, Fibroblast Growth Factor, Type 2* / metabolism ; Stomach Neoplasms* / drug therapy ; Stomach Neoplasms* / genetics ; Stomach Neoplasms* / metabolism ; Stomach Neoplasms* / pathology

Keywords: Biomarkers ; FGFR2b ; Fibroblast growth factor receptor ; Fibroblast growth receptor 2b ; Gastric cancer ; Targeted therapy

Abstract: Gastric and gastroesophageal junction cancer (G/GEJC) is a heterogeneous and complex disease characterized by histologic and molecular subtypes. Although a growing number of treatments have improved survival outcomes in the advanced setting, the greatest therapeutic benefits are observed among patient populations eligible for biomarker-directed therapies. Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) is an emerging biomarker under phase 3 clinical investigation for G/GEJC with the novel monoclonal antibody bemarituzumab. FGFR2b protein overexpression in gastric cancer, together with its function in various oncogenic signaling pathways, makes it an attractive target for precision medicine and thereby has gained clinical interest for its potential prognostic role in G/GEJC. Thus, to explore the potential role of FGFR2b, this narrative review summarizes the role and mechanism of FGFR2b in advanced G/GEJC, describes appropriate detection methodology for FGFR2b protein overexpression, and discusses future considerations for precision treatment in advanced G/GEJC with respect to FGFR2b protein overexpression and the emergence of other biomarkers.