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

Abstract

Background: Gastrointestinal (GI) cancers constitute approximately 25% of cancers worldwide. The fibroblast growth factor receptor (FGFR) family is a promising target for immunotherapy aiming to enhance survival rates. FGFR alterations are associated with GI carcinomas. Their predictive value in different malignancies remains a focus area. While FGFR inhibitors have been approved for cholangiocarcinoma (CC) therapy, uncertainties remain regarding other GI cancers. Methods: A systematic review was conducted using the following databases: CINAHL, Embase, Medline, Cochrane Library, PubMed, and Web of Science. The search terms included “FGFR” and each of the GI malignancies. A total of 18 studies were included in this review. Results: The efficacy of FGFR-targeted therapy is evident. Strong evidence supports the use of FGFR inhibitors in CC, gastro-oesophageal cancer (GC/OC), and hepatocellular cancer, while there is limited evidence for pancreatic cancer (PC) and colorectal cancer (CRC). Alteration forms like FGFR2 fusion or rearrangement are associated with CC, while FGFR2 amplification and FGFR2b overexpression are associated with GC/OC. The administration of multi-kinase inhibitors without prior genomic testing, makes distinct study outcomes not solely attributable to the FGFR blockade. Conclusion: FGFRs have a predictive value for GI cancers. Certain FGFR alterations are predictable for specific GI cancers. The most established FGFR-targeted therapy is for CC. It is essential to expand the FGFR research field for PC and CRC. Consistent molecular diagnostics in clinical trials are vital to comprehend the patient population with the highest efficacy.