A NEW review led by Elizabeth Smyth, National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK, highlights the growing role of fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas.
The gastro oesophageal junction (GOJ) is the point where the oesophagus joins the stomach and is commonly subdivided into three types based on tumour location. Type 1 cancers arise at bottom of the oesophagus, extending up to 1-5cm above the junction, type 2 cancers are located directly at the junction, whilst type 3 cancers originate in the stomach and can extend to the junction. As highlighted by Smyth, gastric cancers remain a global health burden and is the fifth leading cause of cancer-related mortality worldwide, accounting for 660,000 deaths annually.
FGFR2b is a protein involved in cell proliferation, differentiation, angiogenesis, and survival. Its dysregulation has been associated with the progression of several types of cancers, specifically in gastric and gastroesophageal junction cancers.
Currently, bemarituzumab, a first-in-class, humanized, monoclonal antibody is under investigation as a targeted therapy, designed to inhibit the FGFR2b signalling pathway. It has shown clinical promise in early-phase studies, including the Phase 1/2 FIGHT trial, and is now being evaluated in the global Phase 3 FORTITUDE-101 trial, with results anticipated at the ESMO 2025 Annual Meeting.
A landmark global study, led by Rha SY et al., published in January 2025, analysed 3782 fresh or recently obtained (>180 days) tumour samples collected from patients across 37 countries. The study found that 37.8% of patients had any level of FGFR2b overexpression by immunohistochemistry (defined as any tumor cells with 2+ or 3+ staining intensity), while 16.2% met a more stringent criterion of ≥10% tumor cells showing 2+ or 3+ staining.
Overall, this review highlighted the potential of FGFR2b as a targetable biomarker for gastric and gastroesophageal junction cancers.
Reference
Smyth EC et al. FGFR2b protein overexpression: An emerging biomarker in gastric and gastroesophageal junction adenocarcinoma. Cancer Treatment Reviews. 2025;139:102971.
