Abstract
Genomic amplifications and hotspot mutations affecting fibroblast growth factor receptors (FGFRs) have long been recognized as oncogenic drivers across human cancers. However, recent studies have uncovered FGFR in-frame fusions and complex structural variants as an additional class of tumor driver alterations. Notably, the identification of FGFR2 exon 18 truncations and the demonstration of their potent oncogenic competence have refined our understanding of FGFR-driven tumorigenesis and have impacted clinical trial design for FGFR-targeted agents. This review explores the biological and clinical implications of FGFR rearrangements. It covers their mechanisms in driving cancer, their potential as biomarkers to predict treatment response, and the emerging challenges and opportunities for FGFR-targeted therapy. Ultimately, a deeper understanding of FGFR rearrangements is critical for advancing precision oncology and improving patient benefit.