FGFR as a Predictive Marker for Targeted Therapy in Gastrointestinal Malignancies: A Systematic Review

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Gastrointestinal (GI) cancers represent a significant global health burden, accounting for about 25% of all cancer cases worldwide.
• The fibroblast growth factor receptor (FGFR) family is an emerging target for cancer immunotherapy, with potential to improve patient survival rates.
• FGFR alterations are implicated in various GI carcinomas, and their predictive utility across different malignancies is an active area of investigation.

Purpose of the Study:

• To systematically review the existing literature on the role of FGFR alterations and the efficacy of FGFR-targeted therapies in various gastrointestinal cancers.
• To identify specific FGFR alterations associated with different GI cancer types and evaluate the current evidence for FGFR inhibitor efficacy.

Main Methods:

• A comprehensive systematic review was performed utilizing major scientific databases including CINAHL, Embase, Medline, Cochrane Library, PubMed, and Web of Science.
• The search strategy incorporated terms related to "FGFR" and individual GI malignancies.
• A total of 18 relevant studies were included in the final analysis.

Main Results:

• FGFR-targeted therapy demonstrates clear efficacy, with strong evidence supporting its use in cholangiocarcinoma (CC), gastro-oesophageal cancer (GC/OC), and hepatocellular cancer.
• Limited evidence currently exists for the efficacy of FGFR inhibitors in pancreatic cancer (PC) and colorectal cancer (CRC).
• Specific FGFR alterations like FGFR2 fusion/rearrangement are linked to CC, while FGFR2 amplification and FGFR2b overexpression are associated with GC/OC. Some studies used multi-kinase inhibitors without genomic testing, complicating outcome attribution solely to FGFR blockade.

Conclusions:

• Fibroblast growth factor receptors (FGFRs) possess significant predictive value in the context of GI cancers.
• Distinct FGFR alterations serve as biomarkers for specific GI cancer subtypes.
• While FGFR-targeted therapy is well-established for CC, further research is crucial to explore its potential in PC and CRC.
• Standardized molecular diagnostics in clinical trials are essential for identifying patient populations most likely to benefit from FGFR-targeted treatments.